Wikipedia:Wiki Markup Language
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Wiki Mark Up Language (WKML) is a group, started by Nick Irelan, that seeks to create an XML-based format for wikis so that the information they present may be used by third-party programs such as mashups.
This format should be created in a way that allows wikis to be syndicated similar to an RSS feed.
Request to define format and useful attributes
[edit]All editors with XML experience are welcome to comment on how they feel Wikipedia created content such as, but not limited to Infoboxes and Titles should be formatted.
What is the broadly defined structure of any given article?
[edit]All of the common parts of articles should receive special attention to make sure they can be worked with easily by a programmer. For example, the history section would probably be used a lot.
- Title
- Sections
- Categories
- Info boxes (?)
What are the broadly defined attributes of any given article?
[edit]Which, if any, attributes to the articles should be included in WKML?
- Date created
- Updates
Request to define discussion pages format
[edit]All editors with XML experience are welcome to comment on how they feel discussion pages should be formatted.
Basic principles: narrowly or broadly defined?
[edit]All xml formats represent a balance struck between two extremes: the format being defined very narrowly, and the format being defined very broadly. Each approach carries with it a series of advantages and challenges, and it is the job of a format designer to decide which approach's characteristics best suit the way that the format will be used.
Generally speaking, broadly defined formats are more usable, and in particular are more likely to be adopted. One of the reasons for the incredible success of RSS is that it is, eponymously, really simple, and easily expanded. The drawback of a broadly defined format is that it generally requires more work on the part of the developer when the consumer desires a specific application for a document. Consider the following two formats:
Narrow definition
<wikiarticle>
<biography>
<name>George Washington</name>
<content>George Washington was a...</content>
</biography>
</wikiarticle>
Broad definition
<wikiarticle type="Biography" title="George Washington"> <content>George Washington was a...</content> </wikiarticle>
Obviously, the second article can be about anything. This is an advantage in that it fits the extremely loosely-structured nature of Wikipedia, but a disadvantage in that it makes development for specific formats more difficult. Ultimately, defining narrow formats would require articles to conform to templates at the very least, which would drastically limit the scope of articles would could be exposed via WKML. Ultimately, a format which can be applied to any Wikipedia article, no matter how minimally or bizarrely defined, is probably the most appropriate approach. If infobox or template specific information is available, it should be used, but cannot be required.
How the format will be used
[edit]XML exists to be consumed or transformed. A XML document might be consumed by a database in the form of an updategram, which leads to an update of a record in a table, or it might be transformed into a more readable format in the case of an RSS reader.
A pure consumption of the XML involves direct coding against the format, which is typically very narrowly defined. It seems unlikely that much Wikipedia content would be used this way, so this leaves transformation as the end use of WKML.
One approach would be to simply utilize RSS. The problem with this approach is that RSS is probably too broad, and probably doesn't suit the encyclopedic nature of Wikipedia. Ultimately, if RSS was required for a mashup (an RSS feed of new pages, or changes to a page, for example), as long as WKML meets some minimal requirements, it can be transformed into RSS.
A hybrid approach
Indeed, one way to solve this problem of specificity versus simplicity would be separate formats divided along, for example, template lines, with a roll down to a generic article format. This approach has the further advantage that it need not be implemented immediately; a basic WKML format could be created and deployed for widespread use, and then later function as the rolldown format when more specific formats are created. Ultimately, whether the broad or narrow format of the article is used can be an attribute of the request, with the rolldown format as the default for backwards compatibility.
Open questions
[edit]- Are article content and metadata documents separate or are they unified into a single document?
- Content and history are definitely contained in the same document. Documents which represent previous revisions of the document are separate documents, retrieved by a separate syndication / service command.
- What is the broadly defined structure of any given article? (Title, sections, ?)
- The broadly defined structure is as follows:
- root, containing a root document element and some document meta-info such as category information.
- title
- content sections
- history
- The broadly defined structure is as follows:
- What are the broadly defined attributes of any given article?(Title, date created, further date questions feed back into question #1)
- How will infoboxes be handled?
- At this point, it's pretty clear that we have to renotate all of the infobox content.
- How much and how will HTML be scrubbed from the content?
- A general principle which might be helpful is that markup that affects presentation (such as font-strength (bold) or italicization) will be scrubbed without re-notation, while markup that affects actions, such as links, will be renotated in a format that we have to determine. One exception to this will be images, which may need to be renotated, or may simple pass through as is.
Proposed date format
[edit]Wikipedia Markup Language documents use the date format specified in the ISO standard document ISO 8601:1988(E). An important distinction:
Document node values or document attributes which are dates are subject to this standard, dates used in the content are not.
For example:
Standard applies
<wikiarticle linkback="Neuralizer" revisiondate="2007-01-01T16:28:49Z">
Standard does not apply
Brett Bretterson was born at 8:14 PM on Saturday, June 21st, 1954.
Differently grained attributes may require different formats specified within the standard, e.g., some dates may not require time. As per the standard, all times are UTC.
Examples
[edit]Highly developed article in XML format
[edit](In Progress)
<wikiarticle title="DNA">
<template type="sprotect2" />
<template type="otheruses" />
<section id="0">
<link type="internal">Image:DNA Overview.png|thumb|220px|The structure of part of a DNA double helix</link>
'Deoxyribonucleic acid' ('DNA') is a <link type="internal">nucleic acid</link> that contains the <link type="internal">genetics|genetic</link> instructions for the <link type="internal">developmental biology|development</link> and function of <link type="internal">life|living organisms</link>. All living things contain DNA <link type="internal">genome</link>s. A possible exception are a group of <link type="internal">virus</link>es that have <link type="internal">retrovirus|RNA genomes</link>, but viruses are not normally considered as living organisms. The main role of DNA in the <link type="internal">cell (biology)|cell</link> is the long-term storage of information. It is often compared to a <link type="internal">blueprint</link>, since it contains the instructions to construct other components of the cell, such as <link type="internal">protein</link>s and <link type="internal">RNA</link> <link type="internal">molecule</link>s. The DNA segments that carry genetic information are called <link type="internal">gene</link>s, but other DNA sequences have structural purposes, or are involved in regulating the expression of genetic information.
In <link type="internal">eukaryote</link>s such as <link type="internal">animal</link>s and <link type="internal">plant</link>s, DNA is stored inside the <link type="internal">cell nucleus</link>, while in <link type="internal">prokaryote</link>s such as <link type="internal">bacteria</link>, the DNA is in the cell's <link type="internal">cytoplasm</link>. Unlike <link type="internal">enzyme</link>s, DNA does not act directly on other molecules; rather, various enzymes act on DNA and copy its information into either more DNA, in <link type="internal">DNA replication</link>, or <link type="internal">transcription (genetics)|transcribe</link> and <link type="internal">translation (biology)|translate</link> it into protein. In <link type="internal">chromosome</link>s, <link type="internal">chromatin</link> proteins such as <link type="internal">histone</link>s compact and organize DNA, which helps control its interactions with other proteins in the nucleus.
DNA is a long <link type="internal">polymer</link> of simple units called <link type="internal">nucleotide</link>s, which are held together by a backbone made of <link type="internal">carbohydrate|sugars</link> and <link type="internal">phosphate</link> groups. This backbone carries four types of molecules called <link type="internal">nucleobase|bases</link>, and it is the sequence of these four bases that encodes information. The major function of DNA is to encode the sequence of <link type="internal">amino acid residue</link>s in proteins, using the <link type="internal">genetic code</link>. To read the genetic code, cells make a copy of a stretch of DNA in the nucleic acid RNA. These RNA copies can then be used to direct <link type="internal">protein biosynthesis</link>, but they can also be used directly as parts of <link type="internal">ribosome</link>s or <link type="internal">spliceosome</link>s.
</section>
<section id="1" title="Physical and chemical properties">
<link type="image">
<filename>DNA_chemical_structure.png</filename>
<thumb>280px</thumb>
<description>The two strands of DNA are held together by hydrogen bonds between bases. The sugars in the backbone are shown in light blue.</description>
</link>
DNA is a long <link type="internal">polymer</link> made from repeating units called <link type="internal">nucleotide</link>s.<ref name=Alberts>
<cite type="book">
<last>Alberts</last>
<first>Bruce</first>
<coauthors>Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walters</coauthors>
<title>Molecular Biology of the Cell; Fourth Edition</title>
<publisher>Garland Science</publisher>
<date>2002</date>
<location>New York and London</location>
<url>https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mboc4.TOC&depth=2</url>
<id>ISBN 0-8153-3218-1</id>
</cite>
<ref name=Butler>Butler, John M. (2001) Forensic DNA Typing "Elsevier". pp. 14-15. ISBN 978-0-12-147951-0.</ref>
The DNA chain is 22 to 24 <link type="internal"><actual>Ångström</actual><display>angstroms</display></link> wide, and one nucleotide unit is 3.3 angstroms long.
<cite type="journal">
<author>Mandelkern M, Elias J, Eden D, Crothers D</author>
<title>The dimensions of DNA in solution</title>
<journal>J Mol Biol</journal>
<volume>152</volume>
<issue>1</issue>
<pages>153-61</pages>
<year>1981</year>
<id>PMID 7338906</id>
</cite>
Although these repeating units are very small, DNA polymers can be enormous molecules containing millions of nucleotides. For instance, the largest human <link type="internal">chromosome</link> is 220 million <link type="internal">base pair</link>s long.<ref><template type="cite journal | author = Gregory S, et al. | title = The DNA sequence and biological annotation of human chromosome 1 | journal = Nature | volume = 441 | issue = 7091 | pages = 315-21 | year = 2006 | id = PMID 16710414" /></ref>
In living organisms, DNA does not usually exist as a single molecule, but instead as a tightly-associated pair of molecules.<ref name=Watson><template type="cite journal | author = Watson J, Crick F | title = Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid | url=https://profiles.nlm.nih.gov/SC/B/B/Y/W/_/scbbyw.pdf | journal = Nature | volume = 171 | issue = 4356 | pages = 737-8 | year = 1953 | id = PMID 13054692" /></ref><ref name=berg>Berg J., Tymoczko J. and Stryer L. (2002) Biochemistry. W. H. Freeman and Company ISBN 0-7167-4955-6</ref> These two long strands entwine like vines, in the shape of a <link type="internal">helix|double helix</link>. The nucleotide repeats contain both the backbone of the molecule, which holds the chain together, and a base, which interacts with the other DNA strand in the helix. In general, a base linked to a sugar is called a <link type="internal">nucleoside</link> and a base linked to a sugar and one or more phosphate groups is called a <link type="internal">nucleotide</link>. If multiple nucleotides are linked together, as in DNA, this polymer is referred to as a <link type="internal">polynucleotide</link>.
<ref name=IUPAC>
[https://www.chem.qmul.ac.uk/iupac/misc/naabb.html Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents]
IUPAC-IUB Commission on Biochemical Nomenclature (CBN) Accessed 03 Jan 2006
</ref>
The backbone of the DNA strand is made from alternating <link type="internal">phosphate</link> and <link type="internal">carbohydrate|sugar</link> residues.<ref name=Ghosh><template type="cite journal | author = Ghosh A, Bansal M | title = A glossary of DNA structures from A to Z | journal = Acta Crystallogr D Biol Crystallogr | volume = 59 | issue = Pt 4 | pages = 620-6 | year = 2003 | id = PMID 12657780" /></ref> The sugar in DNA is the <link type="internal">pentose</link> (five <link type="internal">carbon</link>) sugar 2-deoxyribose. The sugars are joined together by phosphate groups that form <link type="internal">phosphodiester bond</link>s between the third and fifth carbon <link type="internal">atom</link>s in the sugar rings. These asymmetric <link type="internal">covalent bond|bonds</link> mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand. This arrangement of DNA strands is called antiparallel. The asymmetric ends of a strand of DNA bases are referred to as the <link type="internal">5' end|5'</link> (five prime) and <link type="internal">3' end|3'</link> (three prime) ends. One of the major differences between DNA and RNA is the sugar, with 2-deoxyribose being replaced by the alternative pentose sugar <link type="internal">ribose</link> in RNA.<ref name=berg/>
The DNA double helix is held together by <link type="internal">hydrogen bond</link>s between the bases attached to the two strands. The four bases found in DNA are <link type="internal">adenine</link> (abbreviated A), <link type="internal">cytosine</link> (C), <link type="internal">guanine</link> (G) and <link type="internal">thymine</link> (T). These four bases are shown below and are attached to the sugar/phosphate to form the complete nucleotide, as shown for adenosine monophosphate.
<infotable caption="Structures of the four bases found in DNA and the nucleotide adenosine monophosphate">
<element><link type="image"><filename>Adenine chemical structure.png</filename><width>80px</width></link></element>
<element><link type="image"><filename>Guanine chemical structure.png</filename><width>118px</width></link></element>
<element><link type="image"><filename>Thymine chemical structure.png</filename><width>97px</width></link></element>
<element><link type="image"><filename>Cytosine chemical structure.png</filename><width>75px</width></link></element>
<element><link type="image"><filename>AMP chemical structure.png</filename><width>130px</width></link></element>
<element>-</element>
<element><link type="internal">Adenine</link></element>
<element><link type="internal">Guanine</link></element>
<element><link type="internal">Thymine</link></element>
<element><link type="internal">Cytosine</link></element>
<element><link type="internal">Adenosine monophosphate</link></element>
</infotable>
These bases are classified into two types; adenine and guanine are fused five- and six-membered <link type="internal">heterocyclic compound</link>s called <link type="internal">purine</link>s, while cytosine and thymine are six-membered rings called <link type="internal">pyrimidine</link>s.<ref name=IUPAC/> A fifth pyrimidine base, called <link type="internal">uracil</link> (U), replaces thymine in RNA and differs from thymine by lacking a <link type="internal">methyl group</link> on its ring. Uracil is normally only found in DNA as a breakdown product of cytosine, but a very rare exception to this rule is a <link type="internal">phage|bacterial virus</link> called PBS1 that contains uracil in its DNA.<ref name="nature1963-takahashi"><template type="cite journal | author=Takahashi I, Marmur J. | title=Replacement of thymidylic acid by deoxyuridylic acid in the deoxyribonucleic acid of a transducing phage for Bacillus subtilis | journal=Nature | year=1963 | pages=794-5 | volume=197 | id=PMID 13980287" /></ref>
<link type="Image">:
<filename>DNA orbit animated small.gif</filename>
<description>Structure of a section of DNA. The bases lie horizontally between the two spiralling strands</description>
<ref>
Created from <link type="external>
<url>https://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1D65</url>
<title>PDB 1D65</title>
</ref>
</link>
The double helix is a right-handed spiral. As the DNA strands wind around each other, they leave gaps between each set of phosphate backbones, revealing the sides of the bases inside (see animation). There are two of these grooves twisting around the surface of the double helix: one groove is 22 angstroms wide and the other is 12 angstroms wide.
<cite type="journal">
<author>Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson R</author>
<title> Crystal structure analysis of a complete turn of B-DNA</title>
<journal>Nature</journal>
<volume>287</volume>
<issue>5784</issue>
<pages>755-8</pages>
<year>1980</year>
<id >PMID 7432492</id>
</cite>
The larger groove is called the major groove, while the smaller, narrower groove is called the minor groove. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like <link type="internal">transcription factor</link>s that can bind to specific sequences in double-stranded DNA usually read the sequence by making contacts to the sides of the bases exposed in the major groove.
<cite type="journal">
<author>Pabo C, Sauer R</author>
<title>Protein-DNA recognition</title>
<journal>Annu Rev Biochem</journal>
<volume>53</volume>
<issue />
<pages>293-321</pages>
<year />
<id>PMID 6236744</id>
</cite>
<infotable caption="At top, a 'GC' base pair with three <link type="internal">hydrogen bond</link>s. At the bottom, 'AT' base pair with two hydrogen bonds. Hydrogen bonds are shown as dashed lines.">
<item><link type="image"><filename>GC_Watson_Crick_basepair.png</filename><width>230px</width></link>
<item><link type="image"><filename>AT_Watson_Crick_basepair.png,/filename><width>230px</width></link>
</infotable>
<section id="2" title="Base pairing">
<further>Base pair</further>
Each type of base on one strand forms a bond with just one type of base on the other strand. This is called complementary <link type="internal">base pair</link>ing. Here, purines form <link type="internal">hydrogen bond</link>s to pyrimidines, with A bonding only to T, and C bonding only to G. This arrangement of two nucleotides joined together across the double helix is called a base pair. In a double helix, the two strands are also held together by <link type="internal">force</link>s generated by the <link type="internal">hydrophobic effect</link> and <link type="internal">pi stacking</link>, but these forces are not affected by the sequence of the DNA.<ref><template type="cite journal | author = Ponnuswamy P, Gromiha M | title = On the conformational stability of oligonucleotide duplexes and tRNA molecules | journal = J Theor Biol | volume = 169 | issue = 4 | pages = 419-32 | year = 1994 | id = PMID 7526075" /></ref> As hydrogen bonds are not <link type="internal">covalent bond|covalent</link>, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high <link type="internal">temperature</link>.<ref><template type="cite journal | author = Clausen-Schaumann H, Rief M, Tolksdorf C, Gaub H | title = Mechanical stability of single DNA molecules | url=https://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1300792&blobtype=pdf | journal = Biophys J | volume = 78 | issue = 4 | pages = 1997-2007 | year = 2000 | id = PMID 10733978" /></ref> As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.<ref name=Alberts/>
The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, left). The GC base pair is therefore stronger than the AT base pair. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC content have strongly interacting strands, while short helices with high AT content have weakly interacting strands.<ref><template type="cite journal | author = Chalikian T, Völker J, Plum G, Breslauer K | title = A more unified picture for the thermodynamics of nucleic acid duplex melting: a characterization by calorimetric and volumetric techniques | url=https://www.pubmedcentral.nih.gov/picrender.fcgi?artid=22151&blobtype=pdf | journal = Proc Natl Acad Sci U S A | volume = 96 | issue = 14 | pages = 7853-8 | year = 1999 | id = PMID 10393911" /></ref> Parts of the DNA double helix that need to separate easily, such as the TATAAT <link type="internal">Pribnow box</link> in bacterial <link type="internal">promoter</link>s, tend to have sequences with a high AT content, making the strands easier to pull apart.<ref><template type="cite journal | author = deHaseth P, Helmann J | title = Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase-induced strand separation of double helical DNA | journal = Mol Microbiol | volume = 16 | issue = 5 | pages = 817-24 | year = 1995 | id = PMID 7476180" /></ref> In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their <link type="internal">melting temperature</link> (also called T<sub>m</sub> value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single shape, but some conformations are more stable than others.<ref><template type="cite journal | author = Isaksson J, Acharya S, Barman J, Cheruku P, Chattopadhyaya J | title = Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern | journal = Biochemistry | volume = 43 | issue = 51 | pages = 15996-6010 | year = 2004 | id = PMID 15609994" /></ref> The base pairing, or lack of it, can create various topologies at the <link type="internal">DNA end</link>. These can be exploited in <link type="internal">biotechnology</link>.
</section>
<section id="3" title="Sense and antisense">
<further>Sense (molecular biology)</further>
DNA is copied into RNA by <link type="internal">RNA polymerase</link> enzymes that only work in the 5' to 3' direction.<ref name=Joyce><template type="cite journal | author = Joyce C, Steitz T | title = Polymerase structures and function: variations on a theme? | url=https://www.pubmedcentral.nih.gov/picrender.fcgi?artid=177480&blobtype=pdf | journal = J Bacteriol | volume = 177 | issue = 22 | pages = 6321-9 | year = 1995 | id = PMID 7592405" /></ref> A DNA sequence is called "sense" if its sequence is copied by these enzymes and then translated into protein. The sequence on the opposite strand is complementary to the sense sequence and is therefore called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA. In both prokaryotes and eukaryotes, antisense sequences are transcribed, but the functions of these RNAs are not entirely clear.<ref><template type="cite journal | author = Hüttenhofer A, Schattner P, Polacek N | title = Non-coding RNAs: hope or hype? | journal = Trends Genet | volume = 21 | issue = 5 | pages = 289-97 | year = 2005 | id = PMID 15851066" /></ref> One proposal is that antisense RNAs are involved in regulating <link type="internal">gene expression</link> through RNA-RNA base pairing.<ref><template type="cite journal | author = Munroe S | title = Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns | journal = J Cell Biochem | volume = 93 | issue = 4 | pages = 664-71 | year = 2004 | id = PMID 15389973" /></ref>
A few DNA sequences in prokaryotes and eukaryotes, and more in <link type="internal">plasmid</link>s and <link type="internal">virus</link>es, blur the distinction made above between sense and antisense strands by having overlapping genes.<ref><template type="cite journal | author = Makalowska I, Lin C, Makalowski W | title = Overlapping genes in vertebrate genomes | journal = Comput Biol Chem | volume = 29 | issue = 1 | pages = 1-12 | year = 2005 | id = PMID 15680581" /></ref> In these cases, some DNA sequences do double duty, encoding one protein when read 5' to 3' along one strand, and a second protein when read in the opposite direction (still 5' to 3') along the other strand. In <link type="internal">bacteria</link>, this overlap may be involved in the regulation of gene transcription,<ref><template type="cite journal | author = Johnson Z, Chisholm S | title = Properties of overlapping genes are conserved across microbial genomes | journal = Genome Res | volume = 14 | issue = 11 | pages = 2268-72 | year = 2004 | id = PMID 15520290" /></ref> while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.<ref><template type="cite journal | author = Lamb R, Horvath C | title = Diversity of coding strategies in influenza viruses | journal = Trends Genet | volume = 7 | issue = 8 | pages = 261-6 | year = 1991 | id = PMID 1771674" /></ref> Another way of reducing genome size is seen in some viruses that contain linear or circular single-stranded DNA as their genetic material.<ref><template type="cite journal | author = Davies J, Stanley J | title = Geminivirus genes and vectors | journal = Trends Genet | volume = 5 | issue = 3 | pages = 77-81 | year = 1989 | id = PMID 2660364" /></ref><ref><template type="cite journal | author = Berns K | title = Parvovirus replication | journal = Microbiol Rev | volume = 54 | issue = 3 | pages = 316-29 | year = 1990 | id = PMID 2215424" /></ref>
</section>
<section id="4" title="Supercoiling">
<further>DNA supercoil</further>
DNA can be twisted like a rope in a process called <link type="internal">DNA supercoil</link>ing. Normally, with DNA in its "relaxed" state, a strand circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.<ref><template type="cite journal | author = Benham C, Mielke S | title = DNA mechanics | journal = Annu Rev Biomed Eng | volume = 7 | issue = | pages = 21-53 | year = | id = PMID 16004565" /></ref> If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called <link type="internal">topoisomerase</link>s.<ref name=Champoux><template type="cite journal | author = Champoux J | title = DNA topoisomerases: structure, function, and mechanism | journal = Annu Rev Biochem | volume = 70 | issue = | pages = 369-413 | year = | id = PMID 11395412" /></ref> These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as <link type="internal">transcription (genetics)|transcription</link> and <link type="internal">DNA replication</link>.<ref name=Wang><template type="cite journal | author = Wang J | title = Cellular roles of DNA topoisomerases: a molecular perspective | journal = Nat Rev Mol Cell Biol | volume = 3 | issue = 6 | pages = 430-40 | year = 2002 | id = PMID 12042765" /></ref>
<link type="internal">Image:A-DNA, B-DNA and Z-DNA.png|thumb|right|290px|From left to right, the structures of A, B and Z DNA</link>
</section>
<section id="5" title="Alternative double-helical structures">
<further>Mechanical properties of DNA</further>
DNA exists in several possible conformations. The conformations so far identified are: <link type="internal">A-DNA</link>, B-DNA, C-DNA, D-DNA,<ref name=Hayashi2005><template type="cite journal | author = Hayashi G, Hagihara M, Nakatani K | title = Application of L-DNA as a molecular tag | journal = Nucleic Acids Symp Ser (Oxf) | volume = 49 | pages = 261-262 | year = 2005 | id = PMID 17150733" /></ref> E-DNA,<ref name=Vargason2000><template type="cite journal | author = Vargason JM, Eichman BF, Ho PS | title = The extended and eccentric E-DNA structure induced by cytosine methylation or bromination | journal = Nature Structural Biology | volume = 7 | pages = 758-761 | year = 2000 | id = PMID 10966645" /></ref> H-DNA,<ref name=Wang2006><template type="cite journal | author = Wang G, Vasquez KM | title = Non-B DNA structure-induced genetic instability | journal = Mutat Res | volume = 598 | issue = 1-2 | pages = 103-119 | year = 2006 | id = PMID 16516932" /></ref> L-DNA,<ref name=Hayashi2005><template type="cite journal | author = Hayashi G, Hagihara M, Nakatani K | title = Application of L-DNA as a molecular tag | journal = Nucleic Acids Symp Ser (Oxf) | volume = 49 | pages = 261-262 | year = 2005 | id = PMID 17150733" /></ref> and <link type="internal">Z-DNA</link>.<ref name=Ghosh/><ref><template type="cite journal | author = Palecek E | title = Local supercoil-stabilized DNA structures | journal = Crit Rev Biochem Mol Biol | volume = 26 | issue = 2 | pages = 151-226 | year = 1991 | id = PMID 1914495" /></ref> However, only A-DNA, B-DNA, and Z-DNA are believed to be found in nature. Which conformation DNA adopts depends on the sequence of the DNA, the amount and direction of supercoiling, chemical modifications of the bases and also solution conditions, such as the concentration of <link type="internal">metal</link> <link type="internal">ion</link>s and <link type="internal">polyamine</link>s.<ref><template type="cite journal | author = Basu H, Feuerstein B, Zarling D, Shafer R, Marton L | title = Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies | journal = J Biomol Struct Dyn | volume = 6 | issue = 2 | pages = 299-309 | year = 1988 | id = PMID 2482766" /></ref> Of these three conformations, the "B" form described above is most common under the conditions found in cells. The two alternative double-helical forms of DNA differ in their geometry and dimensions.
The A form is a wider right-handed spiral, with a shallow and wide minor groove and a narrower and deeper major groove. The A form occurs under non-physiological conditions in dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands.<ref><template type="cite journal | author = Wahl M, Sundaralingam M | title = Crystal structures of A-DNA duplexes | journal = Biopolymers | volume = 44 | issue = 1 | pages = 45-63 | year = 1997 | id = PMID 9097733" /></ref> Segments of DNA where the bases have been <link type="internal">methylation|methylated</link> may undergo a larger change in conformation and adopt the <link type="internal">Z-DNA|Z form</link>. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.<ref><template type="cite journal | author = Rothenburg S, Koch-Nolte F, Haag F | title = DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles | journal = Immunol Rev | volume = 184 | issue = | pages = 286-98 | year = | id = PMID 12086319" /></ref>
<link type="internal">Image:Telomere quadruplex.jpg|thumb|left|300px|Structure of a DNA quadruplex formed by <link type="internal">telomere</link> repeats.<ref>Created from [https://ndbserver.rutgers.edu/atlas/xray/structures/U/ud0017/ud0017.html NDB UD0017]</ref></link>
</section>
<section id="6" title="Quadruplex structures">
At the ends of the linear <link type="internal">chromosome</link>s are specialized regions of DNA called <link type="internal">telomere</link>s. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme <link type="internal">telomerase</link>, as normal <link type="internal">DNA polymerase</link>s working on the <link type="internal">lagging strand</link> cannot copy the extreme 3' ends of their DNA templates.<ref name=Greider><template type="cite journal | author = Greider C, Blackburn E | title = Identification of a specific telomere terminal transferase activity in Tetrahymena extracts | journal = Cell | volume = 43 | issue = 2 Pt 1 | pages = 405-13 | year = 1985 | id = PMID 3907856" /></ref> If a chromosome lacked telomeres it would become shorter each time it was replicated. These specialized chromosome caps also help protect the DNA ends from <link type="internal">exonuclease</link>s and stop the <link type="internal">DNA repair</link> systems in the cell from treating them as damage to be corrected.<ref name=Nugent><template type="cite journal | author = Nugent C, Lundblad V | title = The telomerase reverse transcriptase: components and regulation | url=https://www.genesdev.org/cgi/content/full/12/8/1073 | journal = Genes Dev | volume = 12 | issue = 8 | pages = 1073-85 | year = 1998 | id = PMID 9553037" /></ref> In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.<ref><template type="cite journal | author = Wright W, Tesmer V, Huffman K, Levene S, Shay J | title = Normal human chromosomes have long G-rich telomeric overhangs at one end | url=https://www.genesdev.org/cgi/content/full/11/21/2801#B34 | journal = Genes Dev | volume = 11 | issue = 21 | pages = 2801-9 | year = 1997 | id = PMID 9353250" /></ref>
These guanine-rich sequences may stabilise chromosome ends by forming very unusual quadruplex structures. Here, four guanine bases form a flat plate, through hydrogen bonding, and these flat four-base units then stack on top of each other, to form a stable quadruplex.<ref name=Burge><template type="cite journal | author = Burge S, Parkinson G, Hazel P, Todd A, Neidle S | title = Quadruplex DNA: sequence, topology and structure | url=https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17012276 | journal = Nucleic Acids Res | volume = 34 | issue = 19 | pages = 5402-15 | year = 2006 | id = PMID 17012276" /></ref> These structures are often stabilized by <link type="internal">chelation</link> of a metal ion in the centre of each four-base unit. The structure shown to the left is of a quadruplex formed by a DNA sequence containing four consecutive human telomere repeats. The single DNA strand forms a loop, with the sets of four bases stacking in a central quadruplex three plates deep. In the space at the centre of the stacked bases are three chelated <link type="internal">potassium</link> ions.<ref><template type="cite journal | author = Parkinson G, Lee M, Neidle S | title = Crystal structure of parallel quadruplexes from human telomeric DNA | journal = Nature | volume = 417 | issue = 6891 | pages = 876-80 | year = 2002 | id = PMID 12050675" /></ref> Other structures can also be formed and the central set of four bases can come from either one folded strand, or several different parallel strands.
In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a circle stabilized by telomere-binding proteins.<ref><template type="cite journal | author = Griffith J, Comeau L, Rosenfield S, Stansel R, Bianchi A, Moss H, de Lange T | title = Mammalian telomeres end in a large duplex loop | journal = Cell | volume = 97 | issue = 4 | pages = 503-14 | year = 1999 | id = PMID 10338214" /></ref> The very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.<ref name=Burge/>
</section>
</section>
<section id="7" title="Chemical modifications">
<section id="8" title="Regulatory base modifications">
<further>DNA methylation</further>
The expression of genes is influenced by modifications of the bases in DNA. In humans, the most common base modification is <link type="internal">cytosine</link> <link type="internal">methylation</link> to produce <link type="internal">5-Methylcytosine|5-methylcytosine</link>. This modification reduces gene expression and is important in <link type="internal">X-inactivation|X-chromosome inactivation</link>.<ref><template type="cite journal | author = Klose R, Bird A | title = Genomic DNA methylation: the mark and its mediators | journal = Trends Biochem Sci | volume = 31 | issue = 2 | pages = 89-97 | year = 2006 | id = PMID 16403636" /></ref> The level of methylation varies between organisms, with <link type="internal">Caenorhabditis elegans</link> lacking cytosine methylation, while <link type="internal">vertebrate</link>s show high levels, with up to 1% of their DNA being 5-methylcytosine.<ref><template type="cite journal | author = Bird A | title = DNA methylation patterns and epigenetic memory | journal = Genes Dev | volume = 16 | issue = 1 | pages = 6-21 | year = 2002 | id = PMID 11782440" /></ref> Unfortunately, the spontaneous <link type="internal">deamination</link> of 5-methylcytosine produces thymine, and methylated cytosines are therefore <link type="internal">mutation</link> hotspots.<ref><template type="cite journal | author = Walsh C, Xu G | title = Cytosine methylation and DNA repair | journal = Curr Top Microbiol Immunol | volume = 301 | issue = | pages = 283-315 | year = | id = PMID 16570853" /></ref> Other base modifications include adenine methylation in bacteria and the <link type="internal">glycosylation</link> of uracil to produce the "J-base" in <link type="internal">kinetoplastid</link>s
<cite type="journal">
<author>Ratel D, Ravanat J, Berger F, Wion D</author>
<title>N6-methyladenine: the other methylated base of DNA</title>
<journal>Bioessays</journal>
<volume>28</volume>
<issue>3</issue>
<pages>309-15</pages>
<year>2006</year>
<id>PMID 16479578</id>
</cite>
<cite type="journal">
<author>Gommers-Ampt J, Van Leeuwen F, de Beer A, Vliegenthart J, Dizdaroglu M, Kowalak J, Crain P, Borst P</author>
<title>beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei </title>
<journal>Cell</journal>
<volume>75</volume>
<issue>6</issue>
<pages>1129-36</pages>
<year>1993</year>
<id>PMID 8261512</id>
</cite>
</section>
<section id="9" title="DNA damage">
<template type="further|<link type="internal">Mutation</link>" />
<link type="Image"><filename>Benzopyrene DNA adduct 1JDG.png</filename><thumb /><width>250px</width><text>Benzopyrene</text></link>, the major mutagen in <link type="internal">tobacco smoking|tobacco smoke</link>, in an adduct to DNA.<ref>Created from [https://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1JDG PDB 1JDG]</ref></link>
DNA can be damaged by many different sorts of <link type="internal">mutagen</link>s. These include <link type="internal">oxidizing agent</link>s, <link type="internal">alkylating agent</link>s and also high-energy <link type="internal">electromagnetic radiation</link> such as <link type="internal">ultraviolet</link> light and <link type="internal">x-ray</link>s. The type of DNA damage produced depends on the type of mutagen. For example, UV light mostly damages DNA by producing <link type="internal">thymine dimer</link>s, which are cross-links between adjacent pyrimidine bases in a DNA strand.<ref><template type="cite journal | author = Douki T, Reynaud-Angelin A, Cadet J, Sage E | title = Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation | journal = Biochemistry | volume = 42 | issue = 30 | pages = 9221-6 | year = 2003 | id = PMID 12885257" />,</ref> On the other hand, oxidants such as <link type="internal">free radical</link>s or <link type="internal">hydrogen peroxide</link> produce multiple forms of damage, including base modifications, particularly of guanosine, as well as double-strand breaks.<ref><template type="cite journal | author = Cadet J, Delatour T, Douki T, Gasparutto D, Pouget J, Ravanat J, Sauvaigo S | title = Hydroxyl radicals and DNA base damage | journal = Mutat Res | volume = 424 | issue = 1-2 | pages = 9-21 | year = 1999 | id = PMID 10064846" /></ref> It has been estimated that in each human cell, about 500 bases suffer oxidative damage per day.<ref><template type="cite journal | author = Shigenaga M, Gimeno C, Ames B | title = Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage | url=https://www.pnas.org/cgi/reprint/86/24/9697 | journal = Proc Natl Acad Sci U S A | volume = 86 | issue = 24 | pages = 9697-701 | year = 1989 | id = PMID 2602371" /></ref><ref><template type="cite journal | author = Cathcart R, Schwiers E, Saul R, Ames B | title = Thymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage | url=https://www.pnas.org/cgi/reprint/81/18/5633.pdf | journal = Proc Natl Acad Sci U S A | volume = 81 | issue = 18 | pages = 5633-7 | year = 1984 | id = PMID 6592579" /></ref> Of these oxidative lesions, the most dangerous are double-strand breaks, as they can produce <link type="internal">point mutation</link>s, insertions and deletions from the DNA sequence, as well as <link type="internal">chromosomal translocation</link>s.<ref><template type="cite journal | author = Valerie K, Povirk L | title = Regulation and mechanisms of mammalian double-strand break repair | journal = Oncogene | volume = 22 | issue = 37 | pages = 5792-812 | year = 2003 | id = PMID 12947387" /></ref>
Many mutagens <link type="internal">intercalation (chemistry)|intercalate</link> into the space between two adjacent base pairs. These molecules are mostly polycyclic, <link type="internal">aromaticity|aromatic</link>, and planar molecules, and include <link type="internal">ethidium</link>, <link type="internal">proflavin</link>, <link type="internal">daunomycin</link>, <link type="internal">doxorubicin</link> and <link type="internal">thalidomide</link>. DNA intercalators are used in <link type="internal">chemotherapy</link> to inhibit DNA replication in rapidly-growing <link type="internal">cancer</link> cells.<ref><template type="cite journal | author = Braña M, Cacho M, Gradillas A, de Pascual-Teresa B, Ramos A | title = Intercalators as anticancer drugs | journal = Curr Pharm Des | volume = 7 | issue = 17 | pages = 1745-80 | year = 2001 | id = PMID 11562309" /></ref> In order for an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. These structural modifications inhibit <link type="internal">transcription (genetics)|transcription</link> and <link type="internal">DNA replication|replication</link> processes, causing both toxicity and mutations. As a result, DNA intercalators are often <link type="internal">carcinogen</link>s, with <link type="internal">benzopyrene|benzopyrene diol epoxide</link>, <link type="internal">acridine</link>s, <link type="internal">aflatoxin</link> and <link type="internal">ethidium bromide</link> being well-known examples.<ref><template type="cite journal | author = Ferguson L, Denny W | title = The genetic toxicology of acridines | journal = Mutat Res | volume = 258 | issue = 2 | pages = 123-60 | year = 1991 | id = PMID 1881402" /></ref><ref><template type="cite journal | author = Jeffrey A | title = DNA modification by chemical carcinogens | journal = Pharmacol Ther | volume = 28 | issue = 2 | pages = 237-72 | year = 1985 | id = PMID 3936066" /></ref>
==Overview of biological functions==
DNA contains the genetic information that allows living things to function, grow and reproduce. This information is held in the <link type="internal">DNA sequence|sequence</link> of pieces of DNA called <link type="internal">gene</link>s. Genetic information in genes is transmitted through complementary base pairing. For example, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence in a process called transcription. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation. Alternatively, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here we focus on the interactions that happen in these processes between DNA and other molecules.
<link type="internal">Image:RNA pol.jpg|thumb|left|300px|<link type="internal">T7 RNA polymerase</link> producing a mRNA (green) from a DNA template (red and blue). The protein is shown as a purple ribbon.<ref>Created from [https://www.rcsb.org/pdb/explore/explore.do?structureId=1MSW PDB 1MSW]</ref></link>
===Transcription and translation===
<template type="further|<link type="internal">Genetic code</link>, <link type="internal">Transcription (genetics)</link>, <link type="internal">Protein biosynthesis</link>" />
A gene is a sequence of DNA that contains genetic information and can influence the <link type="internal">phenotype</link> of an organism. Within a gene, the sequence of bases along a DNA strand defines a <link type="internal">messenger RNA</link> sequence which then defines a protein sequence. The relationship between the nucleotide sequences of genes and the <link type="internal">amino acid|amino-acid</link> sequences of proteins is determined by the rules of <link type="internal">translation (genetics)|translation</link>, known collectively as the <link type="internal">genetic code</link>. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). In transcription, the codons of a gene are copied into messenger RNA by <link type="internal">RNA polymerase</link>. This RNA copy is then decoded by a <link type="internal">ribosome</link> that reads the RNA sequence by base-pairing the messenger RNA to <link type="internal">transfer RNA</link>, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (<math>4^3</math> combinations). These encode the twenty <link type="internal">list of standard amino acids|standard amino acids</link>. Most amino acids, therefore, have more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA and TAG codons.
<link type="internal">Image:Dnareplication.png|frame|DNA replication. The double helix (blue) is unwound by a <link type="internal">helicase</link>. Next, <link type="internal">DNA polymerase III</link> (green) produces the <link type="internal">leading strand</link> copy (red). A DNA polymerase I molecule (green) binds to the <link type="internal">lagging strand</link>. This enzyme makes discontinuous segments (called <link type="internal">Okazaki fragment</link>s) before <link type="internal">DNA ligase</link> (violet) joins them together.</link>
===Replication===
<template type="further|<link type="internal">DNA replication</link>" />
<link type="internal">Cell division</link> is essential for an organism to grow, but when a cell divides it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for <link type="internal">DNA replication</link>. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called <link type="internal">DNA polymerase</link>. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5' to 3' direction, different mechanisms are used to copy the antiparallel strands of the double helix.<ref><template type="cite journal | author = Albà M | title = Replicative DNA polymerases | url=https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11178285 | journal = Genome Biol | volume = 2 | issue = 1 | pages = REVIEWS3002 | year = 2001 | id = PMID 11178285" /></ref> In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.
==Genes and genomes==
<template type="further|<link type="internal">Cell nucleus</link>, <link type="internal">Gene</link>, <link type="internal">Non-coding DNA</link>" />
DNA is located in the <link type="internal">cell nucleus</link> of eukaryotes, as well as small amounts in <link type="internal">mitochondrion|mitochondria</link> and <link type="internal">chloroplast</link>s. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the <link type="internal">nucleoid</link>.<ref><template type="cite journal | author = Thanbichler M, Wang S, Shapiro L | title = The bacterial nucleoid: a highly organized and dynamic structure | journal = J Cell Biochem | volume = 96 | issue = 3 | pages = 506–21 | year = 2005 | id = PMID 15988757" /></ref> The DNA is usually in linear <link type="internal">chromosome</link>s in eukaryotes, and circular chromosomes in prokaryotes. In the <link type="internal">human genome</link>, there is approximately 3 billion base pairs of DNA arranged into 46 chromosomes.<ref><template type="cite journal | author = Venter J, et al. | title = The sequence of the human genome | journal = Science | volume = 291 | issue = 5507 | pages = 1304-51 | year = 2001 | id = PMID 11181995" /></ref> The genetic information in a genome is held within genes. A gene is a unit of <link type="internal">heredity</link> and is a region of DNA that influences a particular characteristic in an organism. Genes contain an <link type="internal">open reading frame</link> that can be transcribed, as well as <link type="internal">regulatory sequence</link>s such as <link type="internal">promoter</link>s and <link type="internal">enhancer (genetics)|enhancers</link>, which control the expression of the open reading frame.
In many <link type="internal">species</link>, only a small fraction of the total sequence of the <link type="internal">genome</link> encodes protein. For example, only about 1.5% of the human genome consists of protein-coding <link type="internal">exon</link>s, with over 50% of human DNA consisting of non-coding <link type="internal">repeated sequence (DNA)|repetitive sequences</link>.<ref><template type="cite journal | author = Wolfsberg T, McEntyre J, Schuler G | title = Guide to the draft human genome | journal = Nature | volume = 409 | issue = 6822 | pages = 824-6 | year = 2001 | id = PMID 11236998" /></ref> The reasons for the presence of so much <link type="internal">noncoding DNA|non-coding DNA</link> in eukaryotic genomes and the extraordinary differences in <link type="internal">genome size</link>, or <link type="internal">C-value</link>, among species represent a long-standing puzzle known as the "<link type="internal">C-value enigma</link>".<ref><template type="cite journal | author = Gregory T | title = The C-value enigma in plants and animals: a review of parallels and an appeal for partnership | url=https://aob.oxfordjournals.org/cgi/content/full/95/1/133 | journal = Ann Bot (Lond) | volume = 95 | issue = 1 | pages = 133-46 | year = 2005 | id = PMID 15596463" /></ref>
Some non-coding DNA sequences play structural roles in chromosomes. <link type="internal">Telomere</link>s and <link type="internal">centromere</link>s typically contain few genes, but are important for the function and stability of chromosomes.<ref name=Nugent/><ref><template type="cite journal | author = Pidoux A, Allshire R | title = The role of heterochromatin in centromere function | url=https://www.journals.royalsoc.ac.uk/media/804t6y8vmh5utlb6ua5y/contributions/p/x/7/a/px7ahm740dq5ueuk.pdf | journal = Philos Trans R Soc Lond B Biol Sci | volume = 360 | issue = 1455 | pages = 569-79 | year = 2005 | id = PMID 15905142" /></ref> An abundant form of non-coding DNA in humans are <link type="internal">pseudogene</link>s, which are copies of genes that have been disabled by mutation.<ref><template type="cite journal | author = Harrison P, Hegyi H, Balasubramanian S, Luscombe N, Bertone P, Echols N, Johnson T, Gerstein M | title = Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22 | url=https://www.genome.org/cgi/content/full/12/2/272 | journal = Genome Res | volume = 12 | issue = 2 | pages = 272-80 | year = 2002 | id = PMID 11827946" /></ref> These sequences are usually just molecular <link type="internal">fossil</link>s, although they can occasionally serve as raw genetic material for the creation of new genes through the process of <link type="internal">gene duplication</link> and <link type="internal">divergent evolution|divergence</link>.<ref><template type="cite journal | author = Harrison P, Gerstein M | title = Studying genomes through the aeons: protein families, pseudogenes and proteome evolution | journal = J Mol Biol | volume = 318 | issue = 5 | pages = 1155-74 | year = 2002 | id = PMID 12083509" /></ref>
==Interactions with proteins==
All the functions of DNA depend on interactions with proteins. These protein interactions can either be non-specific, or the protein can only bind to a particular DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.
===DNA-binding proteins===
<div class="thumb tleft" style="background-color: #f9f9f9; border: 1px solid #CCCCCC; margin:0.5em;">
{|border="0" width=260px border="0" cellpadding="0" cellspacing="0" style="font-size: 85%; border: 1px solid #CCCCCC; margin: 0.3em;"
|<link type="internal">Image:Nucleosome 2.jpg|260px</link>
|-
|<link type="internal">Image:Nucleosome_(opposites_attracts).JPG|260px</link>
|}
<div style="border: none; width:260px;"><div class="thumbcaption">Interaction of DNA with <link type="internal">histone</link>s (shown in white, top). These proteins' basic amino acids (below left, blue) bind to the acidic phosphate groups on DNA (below right, red).</div></div></div>
Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes between DNA and structural proteins. These proteins organize the DNA into a compact structure called <link type="internal">chromatin</link>. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called <link type="internal">histone</link>s, while in prokaryotes multiple types of proteins are involved.<ref><template type="cite journal | author = Sandman K, Pereira S, Reeve J | title = Diversity of prokaryotic chromosomal proteins and the origin of the nucleosome | journal = Cell Mol Life Sci | volume = 54 | issue = 12 | pages = 1350-64 | year = 1998 | id = PMID 9893710" /></ref> The histones form a disk-shaped complex called a <link type="internal">nucleosome</link>, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making <link type="internal">ionic bond</link>s to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence.<ref><template type="cite journal | author = Luger K, Mäder A, Richmond R, Sargent D, Richmond T | title = Crystal structure of the nucleosome core particle at 2.8 A resolution | journal = Nature | volume = 389 | issue = 6648 | pages = 251-60 | year = 1997 | id = PMID 9305837" /></ref> Chemical modifications of these basic amino acid residues include <link type="internal">methylation</link>, <link type="internal">phosphorylation</link> and <link type="internal">acetylation</link>.<ref><template type="cite journal | author = Jenuwein T, Allis C | title = Translating the histone code | journal = Science | volume = 293 | issue = 5532 | pages = 1074-80 | year = 2001 | id = PMID 11498575" /></ref> These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to <link type="internal">transcription factor</link>s and changing the rate of transcription.<ref><template type="cite journal | author = Ito T | title = Nucleosome assembly and remodelling | journal = Curr Top Microbiol Immunol | volume = 274 | issue = | pages = 1-22 | year = | id = PMID 12596902" /></ref> Other non-specific DNA-binding proteins found in chromatin include the high-mobility group proteins, which bind preferentially to bent or distorted DNA.<ref><template type="cite journal | author = Thomas J | title = HMG1 and 2: architectural DNA-binding proteins | journal = Biochem Soc Trans | volume = 29 | issue = Pt 4 | pages = 395-401 | year = 2001 | id = PMID 11497996" /></ref> These proteins are important in bending arrays of nucleosomes and arranging them into more complex chromatin structures.<ref><template type="cite journal | author = Grosschedl R, Giese K, Pagel J | title = HMG domain proteins: architectural elements in the assembly of nucleoprotein structures | journal = Trends Genet | volume = 10 | issue = 3 | pages = 94-100 | year = 1994 | id = PMID 8178371" /></ref>
A distinct group of DNA-binding proteins are the single-stranded DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-characterised member of this family and is essential for most processes where the double helix is separated, including DNA replication, recombination and DNA repair.<ref><template type="cite journal | author = Iftode C, Daniely Y, Borowiec J | title = Replication protein A (RPA): the eukaryotic SSB | journal = Crit Rev Biochem Mol Biol | volume = 34 | issue = 3 | pages = 141-80 | year = 1999 | id = PMID 10473346" /></ref> These binding proteins seem to stabilize single-stranded DNA and protect it from forming <link type="internal">stem loop</link>s or being degraded by <link type="internal">nuclease</link>s.
<link type="internal">Image:Lambda repressor 1LMB.png|thumb|right|185px|The lambda repressor <link type="internal">helix-turn-helix</link> transcription factor bound to its DNA target<ref>Created from [https://www.rcsb.org/pdb/explore/explore.do?structureId=1LMB PDB 1LMB]</ref></link>
In contrast, other proteins have evolved to specifically bind particular DNA sequences. The most intensively studied of these are the various classes of <link type="internal">transcription factor</link>s. These proteins control gene transcription. Each one of these proteins bind to one particular set of DNA sequences and thereby activates or inhibits the transcription of genes with these sequences close to their <link type="internal">promoter</link>s. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.<ref><template type="cite journal | author = Myers L, Kornberg R | title = Mediator of transcriptional regulation | journal = Annu Rev Biochem | volume = 69 | issue = | pages = 729-49 | year = | id = PMID 10966474" /></ref> Alternatively, transcription factors can bind <link type="internal">enzyme</link>s that modify the histones at the promoter; this will change the accessibility of the DNA template to the polymerase.<ref><template type="cite journal | author = Spiegelman B, Heinrich R | title = Biological control through regulated transcriptional coactivators | journal = Cell | volume = 119 | issue = 2 | pages = 157-67 | year = 2004 | id = PMID 15479634" /></ref>
As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.<ref><template type="cite journal | author = Li Z, Van Calcar S, Qu C, Cavenee W, Zhang M, Ren B | title = A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells | url=https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12808131 | journal = Proc Natl Acad Sci U S A | volume = 100 | issue = 14 | pages = 8164-9 | year = 2003 | id = PMID 12808131" /></ref> Consequently, these proteins are often the targets of the <link type="internal">signal transduction</link> processes that mediate responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base interactions are made in the major groove, where the bases are most accessible.<ref><template type="cite journal | author = Pabo C, Sauer R | title = Protein-DNA recognition | journal = Annu Rev Biochem | volume = 53 | issue = | pages = 293-321 | year = | id = PMID 6236744" /></ref>
<link type="internal">Image:EcoRV 1RVA.png|thumb|left|250px|The <link type="internal">restriction enzyme</link> <link type="internal">EcoRV</link> (green) in a complex with its substrate DNA<ref>Created from [https://www.rcsb.org/pdb/explore/explore.do?structureId=1RVA PDB 1RVA]</ref></link>
===DNA-modifying enzymes===
====Nucleases and ligases====
Nucleases are <link type="internal">enzyme</link>s that cut DNA strands by catalyzing the <link type="internal">hydrolysis</link> of the <link type="internal">phosphodiester bond</link>s. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called <link type="internal">exonuclease</link>s, while <link type="internal">endonuclease</link>s cut within strands. The most frequently-used nucleases in <link type="internal">molecular biology</link> are the <link type="internal">restriction enzyme|restriction endonucleases</link>, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5'-GAT|ATC-3' and makes a cut at the vertical line. In nature, these enzymes protect <link type="internal">bacteria</link> against <link type="internal">phage</link> infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the <link type="internal">restriction modification system</link>.<ref><template type="cite journal | author = Bickle T, Krüger D | title = Biology of DNA restriction | url=https://www.pubmedcentral.nih.gov/picrender.fcgi?artid=372918&blobtype=pdf | journal = Microbiol Rev | volume = 57 | issue = 2 | pages = 434-50 | year = 1993 | id = PMID 8336674" /></ref> In technology, these sequence-specific nucleases are used in <link type="internal">clone (genetics)|molecular cloning</link> and <link type="internal">DNA fingerprinting</link>.
Enzymes called <link type="internal">DNA ligase</link>s can rejoin cut or broken DNA strands, using the energy from either <link type="internal">adenosine triphosphate</link> or <link type="internal">nicotinamide adenine dinucleotide</link>.<ref name=Doherty><template type="cite journal | author = Doherty A, Suh S | title = Structural and mechanistic conservation in DNA ligases. | url=https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11058099 | journal = Nucleic Acids Res | volume = 28 | issue = 21 | pages = 4051-8 | year = 2000 | id = PMID 11058099" /></ref> Ligases are particularly important in <link type="internal">lagging strand</link> DNA replication, as they join together the short segments of DNA produced at the <link type="internal">replication fork</link> into a complete copy of the DNA template. They are also used in <link type="internal">DNA repair</link> and <link type="internal">genetic recombination</link>.<ref name=Doherty/>
====Topoisomerases and helicases====
<link type="internal">Topoisomerase</link>s are enzymes with both nuclease and ligase activity. These proteins change the amount of <link type="internal">DNA supercoil|supercoiling</link> in DNA. Some of these enzyme work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break.<ref name=Champoux/> Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.<ref><template type="cite journal | author = Schoeffler A, Berger J | title = Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism | journal = Biochem Soc Trans | volume = 33 | issue = Pt 6 | pages = 1465-70 | year = 2005 | id = PMID 16246147" /></ref> Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.<ref name=Wang/>
Helicases are proteins that are a type of <link type="internal">molecular motor</link>. They use the chemical energy in <link type="internal">adenosine triphosphate</link> to break the hydrogen bonds between bases and unwind a DNA double helix into single strands.<ref><template type="cite journal | author = Tuteja N, Tuteja R | title = Unraveling DNA helicases. Motif, structure, mechanism and function | url=https://www.blackwell-synergy.com/links/doi/10.1111%2Fj.1432-1033.2004.04094.x | journal = Eur J Biochem | volume = 271 | issue = 10 | pages = 1849-63 | year = 2004 | id = PMID 15128295" /></ref> These enzymes are essential for most processes where enzymes need to access the DNA bases.
====Polymerases====
Polymerases are enzymes that synthesise polynucleotide chains from <link type="internal">nucleoside triphosphate</link>s. They function by adding nucleotides onto the 3' <link type="internal">hydroxyl|hydroxyl group</link> of the previous nucleotide in the DNA strand. As a consequence, all polymerases work in a 5' to 3' direction.<ref name=Joyce/> In the <link type="internal">active site</link> of these enzymes, the nucleoside triphosphate substrate base-pairs to a single-stranded polynucleotide template: this allows polymerases to accurately synthesise the complementary strand of this template. Polymerases are classified depending of the type of template they use.
In <link type="internal">DNA replication</link>, a DNA-dependent <link type="internal">DNA polymerase</link> make a DNA copy of a DNA sequence. Accuracy is vital in this process, so many of these polymerases have a <link type="internal">Proofreading#Proofreading in biology|proofreading</link> activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3' to 5' <link type="internal">exonuclease</link> activity is activated and the incorrect base removed.<ref><template type="cite journal | author = Hubscher U, Maga G, Spadari S | title = Eukaryotic DNA polymerases | journal = Annu Rev Biochem | volume = 71 | issue = | pages = 133-63 | year = | id = PMID 12045093" /></ref> In most organisms DNA polymerases function in a large complex called the <link type="internal">replisome</link> that contains multiple accessory subunits, such as the <link type="internal">DNA clamp</link> or <link type="internal">helicase</link>s.<ref><template type="cite journal | author = Johnson A, O'Donnell M | title = Cellular DNA replicases: components and dynamics at the replication fork | journal = Annu Rev Biochem | volume = 74 | issue = | pages = 283-315 | year = | id = PMID 15952889" /></ref>
RNA-dependent DNA polymerases are a specialised class of polymerases that copy the sequence of a RNA strand into DNA. They include <link type="internal">reverse transcriptase</link>, which is a <link type="internal">virus|viral</link> enzyme involved in the infection of cells by <link type="internal">retrovirus</link>es, and <link type="internal">telomerase</link>, which is required for the replication of <link type="internal">telomere</link>s.<ref><template type="cite journal | author = Tarrago-Litvak L, Andréola M, Nevinsky G, Sarih-Cottin L, Litvak S | title = The reverse transcriptase of HIV-1: from enzymology to therapeutic intervention | url=https://www.fasebj.org/cgi/reprint/8/8/497 | journal = FASEB J | volume = 8 | issue = 8 | pages = 497-503 | year = 1994 | id = PMID 7514143" /></ref><ref name=Greider/> Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.<ref name=Nugent/>
Transcription is carried out by a DNA-dependent <link type="internal">RNA polymerase</link> that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a <link type="internal">promoter</link> and separates the DNA strands. It then copies the gene sequence into a <link type="internal">messenger RNA</link> transcript until it reaches a region of DNA called the <link type="internal">terminator (genetics)|terminator</link>, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.<ref><template type="cite journal | author = Martinez E | title = Multi-protein complexes in eukaryotic gene transcription | journal = Plant Mol Biol | volume = 50 | issue = 6 | pages = 925-47 | year = 2002 | id = PMID 12516863" /></ref>
==Genetic recombination==
<div class="thumb tright" style="background-color: #f9f9f9; border: 1px solid #CCCCCC; margin:0.5em;">
{|border="0" width=250px border="0" cellpadding="0" cellspacing="0" style="font-size: 85%; border: 1px solid #CCCCCC; margin: 0.3em;"
|<link type="internal">Image:Holliday Junction cropped.png|250px</link>
|-
|<link type="internal">Image:Holliday junction coloured.png|250px</link>
|}
<div style="border: none; width:250px;"><div class="thumbcaption">Structure of the <link type="internal">Holliday junction</link> intermediate in <link type="internal">genetic recombination</link>. The four separate DNA strands are coloured red, blue, green and yellow.<ref>Created from [https://www.rcsb.org/pdb/explore/explore.do?structureId=1M6G PDB 1M6G]</ref></div></div></div>
<template type="further|<link type="internal">Genetic recombination</link>" />
<link type="internal">Image:Chromosomal Recombination.svg|thumb|250px|left|Recombination involves the breakage and rejoining of two chromosomes (M and F) to produce two re-arranged chromosomes (C1 and C2).</link>
A DNA helix does not usually interact with other segments of DNA, and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".<ref><template type="cite journal | author = Cremer T, Cremer C | title = Chromosome territories, nuclear architecture and gene regulation in mammalian cells | journal = Nat Rev Genet | volume = 2 | issue = 4 | pages = 292-301 | year = 2001 | id = PMID 11283701" /></ref> This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is when they <link type="internal">genetic recombination|recombine</link>. Recombination is when two DNA helices break, swap a section and then rejoin. In eukaryotes this process usually occurs during <link type="internal">meiosis</link>, when the two sister <link type="internal">chromatid</link>s are paired together in the center of the cell. Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of <link type="internal">selection</link> and can be important in the rapid evolution of new proteins.<ref><template type="cite journal | author = Pál C, Papp B, Lercher M | title = An integrated view of protein evolution | journal = Nat Rev Genet | volume = 7 | issue = 5 | pages = 337-48 | year = 2006 | id = PMID 16619049" /></ref> Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.<ref><template type="cite journal | author = O'Driscoll M, Jeggo P | title = The role of double-strand break repair - insights from human genetics | journal = Nat Rev Genet | volume = 7 | issue = 1 | pages = 45-54 | year = 2006 | id = PMID 16369571" /></ref>
The most common form of recombination is <link type="internal">chromosomal crossover|homologous recombination</link>, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce <link type="internal">chromosomal translocation</link>s and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as <link type="internal">Cre recombinase</link>.<ref><template type="cite journal | author = Ghosh K, Van Duyne G | title = Cre-loxP biochemistry | journal = Methods | volume = 28 | issue = 3 | pages = 374-83 | year = 2002 | id = PMID 12431441" /></ref> In the first step, the recombinase creates a nick in one strand of a DNA double helix, allowing the nicked strand to pull apart from its <link type="internal">complementarity (molecular biology)|complementary</link> strand and <link type="internal">annealing (biology)|anneal</link> to one strand of the double helix on the opposite chromatid. A second nick allows the strand in the second chromatid to pull apart and anneal to the remaining strand in the first helix, forming a structure known as a cross-strand exchange or a <link type="internal">Holliday junction</link>. The Holliday junction is a tetrahedral junction structure which can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.<ref><template type="cite journal | author = Dickman M, Ingleston S, Sedelnikova S, Rafferty J, Lloyd R, Grasby J, Hornby D | title = The RuvABC resolvasome | journal = Eur J Biochem | volume = 269 | issue = 22 | pages = 5492-501 | year = 2002 | id = PMID 12423347" /></ref>
==Uses in technology==
===Forensics ===
<template type="further|<link type="internal">Genetic fingerprinting</link>" />
<link type="internal">Forensic science|Forensic scientists</link> can use DNA in <link type="internal">blood</link>, <link type="internal">semen</link>, <link type="internal">skin</link>, <link type="internal">saliva</link> or <link type="internal">hair</link> at a crime scene to identify a perpetrator. This process is called <link type="internal">genetic fingerprinting</link>, or more accurately, DNA profiling. In DNA profiling, the lengths of variable sections of repetitive DNA, such as <link type="internal">short tandem repeat</link>s and <link type="internal">minisatellite</link>s, are compared between people. This method is usually an extremely reliable technique for identifying a criminal.<ref><template type="cite journal | author = Collins A, Morton N | title = Likelihood ratios for DNA identification | url=https://www.pnas.org/cgi/reprint/91/13/6007.pdf | journal = Proc Natl Acad Sci U S A | volume = 91 | issue = 13 | pages = 6007-11 | year = 1994 | id = PMID 8016106" /></ref> However, identification can be complicated if the scene is contaminated with DNA from several people.<ref><template type="cite journal | author = Weir B, Triggs C, Starling L, Stowell L, Walsh K, Buckleton J | title = Interpreting DNA mixtures | journal = J Forensic Sci | volume = 42 | issue = 2 | pages = 213-22 | year = 1997 | id = PMID 9068179" /></ref> DNA profiling was developed in 1984 by British geneticist Sir <link type="internal">Alec Jeffreys</link>,<ref><template type="cite journal | author = Jeffreys A, Wilson V, Thein S | title = Individual-specific 'fingerprints' of human DNA. | journal = Nature | volume = 316 | issue = 6023 | pages = 76-9 | year = | id = PMID 2989708" /></ref> and first used in forensic science to convict Colin Pitchfork in the 1988 <link type="internal">Enderby murders</link> case.<ref>[https://www.forensic.gov.uk/forensic_t/inside/news/list_casefiles.php?case=1 Colin Pitchfork - first murder conviction on DNA evidence also clears the prime suspect] Forensic Science Service Accessed 23 Dec 2006</ref> People convicted of certain types of crimes may be required to provide a sample of DNA for a database. This has helped investigators solve old cases where only a DNA sample was obtained from the scene. DNA profiling can also be used to identify victims of mass casualty incidents.<ref><template type="cite web |url=https://massfatality.dna.gov/Introduction/ |title=DNA Identification in Mass Fatality Incidents |date=September 2006 |publisher=National Institute of Justice" /></ref>
===Bioinformatics===
<template type="further|<link type="internal">Bioinformatics</link>" />
<link type="internal">Bioinformatics</link> involves the manipulation, searching, and <link type="internal">data mining</link> of DNA sequence data. The development of techniques to store and search DNA sequences have led to widely-applied advances in <link type="internal">computer science</link>, especially <link type="internal">string searching algorithm</link>s, <link type="internal">machine learning</link> and <link type="internal">database theory</link>.<ref>Baldi, Pierre. Brunak, Soren. Bioinformatics: The Machine Learning Approach MIT Press (2001) ISBN 978-0-262-02506-5</ref> String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, was developed to search for specific sequences of nucleotides.<ref>Gusfield, Dan. Algorithms on Strings, Trees, and Sequences: Computer Science and Computational Biology. Cambridge University Press, 15 January <link type="internal">1997</link>. ISBN 978-0-521-58519-4.</ref> In other applications such as <link type="internal">text editor</link>s, even simple algorithms for this problem usually suffice, but DNA sequences cause these algorithms to exhibit near-worst-case behaviour due to their small number of distinct characters. The related problem of <link type="internal">sequence alignment</link> aims to identify <link type="internal">homology (biology)|homologous</link> sequences and locate the specific <link type="internal">mutation</link>s that make them distinct. These techniques, especially <link type="internal">multiple sequence alignment</link>, are used in studying <link type="internal">phylogenetics|phylogenetic</link> relationships and protein function.<ref><template type="cite journal | author = Sjölander K | title = Phylogenomic inference of protein molecular function: advances and challenges | url=https://bioinformatics.oxfordjournals.org/cgi/reprint/20/2/170 | journal = Bioinformatics | volume = 20 | issue = 2 | pages = 170-9 | year = 2004 | id = PMID 14734307" /></ref> Data sets representing entire genomes' worth of DNA sequences, such as those produced by the <link type="internal">Human Genome Project</link>, are difficult to use without annotations, which label the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by <link type="internal">gene finding</link> algorithms, which allow researchers to predict the presence of particular <link type="internal">gene product</link>s in an organism even before they have been isolated experimentally.<ref name="Mount"><template type="cite book|author = Mount DM | title = Bioinformatics: Sequence and Genome Analysis | edition = 2 | publisher = Cold Spring Harbor Laboratory Press | location | Cold Spring Harbor, NY | date = 2004 | isbn = 0879697121" /></ref>
===DNA and computation ===
<template type="further|<link type="internal">DNA computing</link>" />
DNA was first used in computing to solve a small version of the directed <link type="internal">Hamiltonian path problem</link>, an <link type="internal">NP-complete</link> problem.<ref><template type="cite journal | author = Adleman L | title = Molecular computation of solutions to combinatorial problems | journal = Science | volume = 266 | issue = 5187 | pages = 1021-4 | year = 1994 | id = PMID 7973651" /></ref> <link type="internal">DNA computing</link> is advantageous over electronic computers in power use, space use, and efficiency, due to its ability to compute in a highly parallel fashion (see <link type="internal">parallel computing</link>). A number of other problems, including simulation of various <link type="internal">abstract machine</link>s, the <link type="internal">boolean satisfiability problem</link>, and the bounded version of the <link type="internal">travelling salesman problem</link>, have since been analysed using DNA computing.<ref><template type="cite journal | author = Parker J | title = Computing with DNA. | url=https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12524509 | journal = EMBO Rep | volume = 4 | issue = 1 | pages = 7-10 | year = 2003 | id = PMID 12524509" /></ref> Due to its compactness, DNA also has a theoretical role in <link type="internal">cryptography</link>, where in particular it allows unbreakable <link type="internal">one-time pad</link>s to be efficiently constructed and used.<ref>Ashish Gehani, Thomas LaBean and John Reif. [https://citeseer.ist.psu.edu/gehani99dnabased.html DNA-Based Cryptography].
Proceedings of the 5th DIMACS Workshop on DNA Based Computers, Cambridge, MA, USA, 14 – 15 June 1999.</ref>
===History and anthropology===
<template type="further|<link type="internal">Phylogenetics</link> and <link type="internal">Genetic genealogy</link>" />
Because DNA collects mutations over time, which are then inherited, it contains historical information and by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their <link type="internal">phylogeny</link>.<ref><template type="cite journal | author = Wray G | title = Dating branches on the tree of life using DNA | url=https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11806830 | journal = Genome Biol | volume = 3 | issue = 1 | pages = REVIEWS0001 | year = 2002 | id = PMID 11806830" /></ref> This field of <link type="internal">phylogenetics</link> is a powerful tool in <link type="internal">evolutionary biology</link>. If DNA sequences within a species are compared, <link type="internal">population genetics|population geneticists</link> can learn the history of particular populations. This can be used in studies ranging from <link type="internal">ecological genetics</link> to <link type="internal">anthropology</link>; for example, DNA evidence is being used to try to identify the <link type="internal">Ten Lost Tribes of Israel</link>.<ref>Lost Tribes of Israel, <link type="internal">NOVA (TV series)|NOVA</link>, PBS airdate: 22 February 2000. Transcript available from [https://www.pbs.org/wgbh/nova/transcripts/2706israel.html PBS.org,] (last accessed on 4 March 2006)</ref><ref>Kleiman, Yaakov. [https://www.aish.com/societywork/sciencenature/the_cohanim_-_dna_connection.asp "The Cohanim/DNA Connection: The fascinating story of how DNA studies confirm an ancient biblical tradition".] aish.com (January 13, 2000). Accessed 4 March 2006.</ref>
DNA has also been used to look at modern family relationships, such as establishing family relationships between the descendants of <link type="internal">Sally Hemings</link> and <link type="internal">Thomas Jefferson</link>. This usage is closely related to the use of DNA in criminal investigations detailed above. Indeed, some criminal investigations have been solved when DNA from crime scenes has matched relatives of the guilty individual.<ref>Bhattacharya, Shaoni. [https://www.newscientist.com/article.ns?id=dn4908 "Killer convicted thanks to relative's DNA".] newscientist.com (20 April 2004). Accessed 22 Dec 06</ref>
==History==
<link type="internal">Image:Francis Crick.png|thumb|right|<link type="internal">Francis Crick</link></link>
<link type="internal">Image:JamesWatson.jpg|thumb|<link type="internal">James D. Watson|James Watson</link> in the <link type="internal">Cavendish Laboratory</link> at the <link type="internal">University of Cambridge</link></link>
<template type="further|<link type="internal">History of molecular biology</link>" />
DNA was first isolated by <link type="internal">Friedrich Miescher</link> who, in 1869, discovered a microscopic substance in the <link type="internal">pus</link> of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".<ref><template type="cite journal | author = Dahm R | title = Friedrich Miescher and the discovery of DNA | journal = Dev Biol | volume = 278 | issue = 2 | pages = 274-88 | year = 2005 | id = PMID 15680349" /></ref>
In 1929 this discovery was followed by <link type="internal">Phoebus Levene</link>'s identification of the base, sugar and phosphate nucleotide unit.<ref><template type="cite journal | author = Levene P, | title = The structure of yeast nucleic acid | url=https://www.jbc.org/cgi/reprint/40/2/415 | journal = J Biol Chem | volume = 40 | issue = 2 | pages = 415-24 | year = 1919" /></ref> Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However, Levene thought the chain was short and the bases repeated in a fixed order. In 1937 <link type="internal">William Astbury</link> produced the first <link type="internal">X-ray diffraction</link> patterns that showed that DNA had a regular structure.<ref><template type="cite journal | author =Astbury W, | title = Nucleic acid | journal = Symp. SOC. Exp. Bbl | volume = 1 | issue = 66 | year = 1947" /></ref>
In 1943, <link type="internal">Oswald Theodore Avery</link> discovered that <link type="internal">trait (biology)|traits</link> of the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. Avery identified DNA as this <link type="internal">transforming principle</link>.<ref><template type="cite journal | author = Avery O, MacLeod C, McCarty M | title = Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Inductions of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III | url=https://www.jem.org/cgi/reprint/149/2/297 | journal = J Exp Med | volume = 149 | issue = 2 | pages = 297-326 | year = 1979 | id = PMID 33226" /></ref> DNA's role in <link type="internal">heredity</link> was confirmed in 1953, when <link type="internal">Alfred Hershey</link> and <link type="internal">Martha Chase</link> in the <link type="internal">Hershey-Chase experiment</link> showed that DNA is the <link type="internal">genetic material</link> of the <link type="internal">T2 phage</link>.<ref><template type="cite journal | author = Hershey A, Chase M | title = Independent functions of viral protein and nucleic acid in growth of bacteriophage | url=https://www.jgp.org/cgi/reprint/36/1/39.pdf | journal = J Gen Physiol | volume = 36 | issue = 1 | pages = 39-56 | year = 1952 | id = PMID 12981234" /></ref>
Using <link type="internal">X-ray diffraction</link> data from <link type="internal">Rosalind Franklin</link> and the information that the bases were paired, <link type="internal">James D. Watson</link> and <link type="internal">Francis Crick</link> produced the first accurate model of DNA structure in 1953 in their article <link type="internal">Molecular structure of Nucleic Acids|The Molecular structure of Nucleic Acids</link>.<ref name=Watson/> Watson and Crick proposed the <link type="internal">central dogma of molecular biology</link> in 1957, describing how proteins are produced from <link type="internal">cell nucleus|nucleic</link> DNA. In 1962 Watson, Crick, and <link type="internal">Maurice Wilkins</link> jointly received the <link type="internal">Nobel Prize</link> in <link type="internal">Nobel Prize in Physiology or Medicine|Physiology or Medicine</link>.<ref>[https://nobelprize.org/nobel_prizes/medicine/laureates/1962/ The Nobel Prize in Physiology or Medicine 1962] Nobelprize.org Accessed 22 Dec 06</ref>
In an influential presentation in 1957, Crick laid out the "Central Dogma", which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".<ref>Crick, F.H.C. [https://genome.wellcome.ac.uk/assets/wtx030893.pdf On degenerate templates and the adaptor hypothesis (PDF).] genome.wellcome.ac.uk (Lecture, 1955). Accessed 22 Dec 2006</ref> Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the <link type="internal">Meselson-Stahl experiment</link>.<ref><template type="cite journal | author = Meselson M, Stahl F | title = The replication of DNA in Escherichia coli | journal = Proc Natl Acad Sci U S A | volume = 44 | issue = 7 | pages = 671-82 | year = 1958 | id = PMID 16590258" /></ref> Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing <link type="internal">Har Gobind Khorana</link>, <link type="internal">Robert W. Holley</link> and <link type="internal">Marshall Warren Nirenberg</link> to decipher the <link type="internal">genetic code</link>.<ref>[https://nobelprize.org/nobel_prizes/medicine/laureates/1968/ The Nobel Prize in Physiology or Medicine 1968] Nobelprize.org Accessed 22 Dec 06</ref> These findings represent the birth of <link type="internal">molecular biology</link>.
==References==
<div class="references-small" style="-moz-column-count:2; column-count:2;">
<references/>
</div>
==Further reading==
<list>
<item> Clayton, Julie. (Ed.). 50 Years of DNA, Palgrave MacMillan Press, 2003. ISBN 978-1-40-391479-8</item>
<item> Judson, Horace Freeland. The Eighth Day of Creation: Makers of the Revolution in Biology, Cold Spring Harbor Laboratory Press, 1996. ISBN 978-0-87-969478-4</item>
<item> <link type="internal">Robert Olby|Olby, Robert</link>. The Path to The Double Helix: Discovery of DNA, first published in October 1974 by MacMillan, with foreword by Francis Crick; ISBN 978-0-48-668117-7; the definitive DNA textbook, revised in 1994, with a 9 page postscript.</item>
<item> <link type="internal">Matt Ridley|Ridley, Matt</link>. Francis Crick: Discoverer of the Genetic Code (Eminent Lives) first published in June 2006 in the USA and then to be in the UK September 2006, by HarperCollins Publishers; 192 pp, ISBN 978-0-06-082333-7
<item> Rose, Steven. The Chemistry of Life, Penguin, ISBN 978-0-14-027273-4</item>.
<item> Watson, James D. and Francis H.C. Crick. [https://www.nature.com/nature/dna50/watsoncrick.pdf A structure for Deoxyribose Nucleic Acid] (PDF). <link type="internal">Nature (journal)|Nature</link> 171, 737 – 738, <link type="internal">25 April</link> <link type="internal">1953</link>.</item>
<item> Watson, James D. DNA: The Secret of Life ISBN 978-0-375-41546-3.</item>
<item> Watson, James D. <link type="internal">The Double Helix|The Double Helix: A Personal Account of the Discovery of the Structure of DNA (Norton Critical Editions)</link>. ISBN 978-0-393-95075-5</item>
</list>
==External links==
<template type="Spoken Wikipedia|dna.ogg|2007-02-12" />
<template type="commonscat|DNA" />
*[https://www.dnaftb.org/dnaftb/ DNA from the beginning]
*[https://www.nature.com/nature/dna50/archive.html Double helix: 50 years of DNA], <link type="internal">Nature (journal)|Nature</link>
*[https://mason.gmu.edu/~emoody/rfranklin.html Rosalind Franklin's contributions to the study of DNA]
*[https://www.genome.gov/10506367 U.S. National DNA Day] - watch videos and participate in real-time chat with top scientists
*[https://www.genome.gov/10506718 Genetic Education Modules for Teachers] - DNA from the Beginning Study Guide
*[https://www.bbc.co.uk/bbcfour/audiointerviews/profilepages/crickwatson1.shtml Listen to Francis Crick and James Watson talking on the BBC in 1962, 1972, and 1974]
*[https://www.dnakin.com Using DNA in Genealogical Research]
*[https://www.dnai.org DNA Interactive] (requires <link type="internal">Adobe Flash</link>)
*[https://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb23_1.html DNA: RCSB PDB Molecule of the Month]
*[https://www.fidelitysystems.com/Unlinked_DNA.html DNA under electron microscope]
*<template type="dmoz|Science/Biology/Biochemistry_and_Molecular_Biology/Biomolecules/Nucleic_Acids/DNA/|DNA" />
*[https://dnawiz.com/ DNA Articles] - articles and information collected from various sources
*<template type="McGrawHillAnimation|genetics|Dna%20Replication" />
*[https://biostudio.com/c_%20education%20mac.htm DNA coiling to form chromosomes]
<template type="Nucleic acids" />
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Stub Article in XML Format
[edit]<wikiarticle linkback="Franklin Pierce High School" revisiondate="2007-02-08T20:18:03Z">
<title>Franklin Pierce High School</title>
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<value><link type="external">https://www.fp.k12.wa.us/fphs/</link></value>
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Franklin Pierce High School in <link type="internal">Tacoma, Washington</link> is named after the fourteenth US President, <link type="internal">Franklin Pierce</link>, who was president when the Washington Territory was formed in 1853.
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<section id="1" title="Academics">
<link type="internal">Advanced Placement</link> courses are offered in Calculus AB, Statistics, Chemistry (at Washington H.S.) and US History. Language classses offered are French, Spanish, Japanese, and American Sign Language.
</section>
<section id="2" title="Activies">
Clubs at FPHS are Drama Club, <link type="internal">FBLA</link>, <link type="internal">FFA</link>, <link type="internal">National Honor Society</link>, International Cultures Club, and Ski Club.
</section>
<section id="3" title="Athletics">
Football, Golf, Cross Country, Volleyball, Soccer,Basketball, Wrestling, Tennis, Baseball, Fastpitch Softball, and Track.
<link type="internal">Category:High schools in Washington</link>
<link type="internal">Category:South Puget Sound League</link>
<link type="internal">Category:Educational institutions established in 1952</link>
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[edit]<wikiarticle linkback="Neuralizer" revisiondate="2007-01-01T16:28:49Z">
<title>Neuralizer</title>
<section id="0" Title="">
A neuralizer is a fictional device portrayed in the 1991 movie, Men In Black.
It is used to erase memories of people involved in encounters with extraterrestrials.
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<history />
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