FAMEPedia:Wiki Markup Language

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
All editors with XML experience are welcome to comment on how they feel FAMEPedia created content such as, but not limited to Infoboxes and Titles should be formatted.

What is the broadly defined structure of any given article?
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?
Which, if any, attributes to the articles should be included in WKML?


 * Date created
 * Updates

Request to define discussion pages format
All editors with XML experience are welcome to comment on how they feel discussion pages should be formatted.

Basic principles: narrowly or broadly defined?
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

George Washington George Washington was a...

Broad definition

 George Washington was a...

Obviously, the second article can be about anything. This is an advantage in that it fits the extremely loosely-structured nature of FAMEPedia, 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 FAMEPedia 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
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 FAMEPedia 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 FAMEPedia. 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

 * 1) Are article content and metadata documents separate or are they unified into a single document?
 * 2) * 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.
 * 3) What is the broadly defined structure of any given article? (Title, sections, ?)
 * 4) * The broadly defined structure is as follows:
 * 5) *# root, containing a root document element and some document meta-info such as category information.
 * 6) *# title
 * 7) *# content sections
 * 8) *# history
 * 9) What are the broadly defined attributes of any given article?(Title, date created, further date questions feed back into question #1)
 * 10) How will infoboxes be handled?
 * 11) *At this point, it's pretty clear that we have to renotate all of the infobox content.
 * 12) How much and how will HTML be scrubbed from the content?
 * 13) * 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
FAMEPedia 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



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
= Highly developed article in XML format =

(In Progress)

 Image:DNA Overview.png|thumb|220px|The structure of part of a DNA double helix 'Deoxyribonucleic acid' ('DNA') is a nucleic acid that contains the genetics|genetic instructions for the developmental biology|development and function of life|living organisms. All living things contain DNA genome s. A possible exception are a group of virus es that have retrovirus|RNA genomes, but viruses are not normally considered as living organisms. The main role of DNA in the cell (biology)|cell is the long-term storage of information. It is often compared to a blueprint, since it contains the instructions to construct other components of the cell, such as protein s and RNA molecule s. The DNA segments that carry genetic information are called gene s, but other DNA sequences have structural purposes, or are involved in regulating the expression of genetic information. In eukaryote s such as animal s and plant s, DNA is stored inside the cell nucleus, while in prokaryote s such as bacteria , the DNA is in the cell's cytoplasm. Unlike enzyme s, DNA does not act directly on other molecules; rather, various enzymes act on DNA and copy its information into either more DNA, in DNA replication, or transcription (genetics)|transcribe and translation (biology)|translate it into protein. In chromosome s, chromatin proteins such as histone s compact and organize DNA, which helps control its interactions with other proteins in the nucleus. DNA is a long polymer of simple units called nucleotide s, which are held together by a backbone made of carbohydrate|sugars and phosphate groups. This backbone carries four types of molecules called nucleobase|bases, and it is the sequence of these four bases that encodes information. The major function of DNA is to encode the sequence of amino acid residue s in proteins, using the genetic code. 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 protein biosynthesis, but they can also be used directly as parts of ribosome s or spliceosome s.	 DNA_chemical_structure.png 280px The two strands of DNA are held together by hydrogen bonds between bases. The sugars in the backbone are shown in light blue. DNA is a long polymer made from repeating units called nucleotide s. The DNA chain is 22 to 24 Ångström  angstroms  wide, and one nucleotide unit is 3.3 angstroms long. Mandelkern M, Elias J, Eden D, Crothers D 			 The dimensions of DNA in solution J Mol Biol 152 			 1 			 153-61 			 1981 			PMID 7338906 Although these repeating units are very small, DNA polymers can be enormous molecules containing millions of nucleotides. For instance, the largest human chromosome is 220 million base pair s long. In living organisms, DNA does not usually exist as a single molecule, but instead as a tightly-associated pair of molecules. These two long strands entwine like vines, in the shape of a helix|double helix. 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 nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. If multiple nucleotides are linked together, as in DNA, this polymer is referred to as a polynucleotide. The backbone of the DNA strand is made from alternating phosphate and carbohydrate|sugar residues. The sugar in DNA is the pentose (five carbon ) sugar 2-deoxyribose. The sugars are joined together by phosphate groups that form phosphodiester bond s between the third and fifth carbon atom s in the sugar rings. These asymmetric covalent bond|bonds 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 5' end|5' (five prime) and 3' end|3' (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 ribose in RNA. The DNA double helix is held together by hydrogen bond s between the bases attached to the two strands. The four bases found in DNA are adenine (abbreviated A), cytosine (C), guanine (G) and thymine (T). These four bases are shown below and are attached to the sugar/phosphate to form the complete nucleotide, as shown for adenosine monophosphate.  Adenine chemical structure.png 80px Guanine chemical structure.png 118px Thymine chemical structure.png 97px Cytosine chemical structure.png 75px AMP chemical structure.png 130px - 			 Adenine Guanine Thymine Cytosine Adenosine monophosphate

These bases are classified into two types; adenine and guanine are fused five- and six-membered heterocyclic compound s called purine s, while cytosine and thymine are six-membered rings called pyrimidine s. A fifth pyrimidine base, called uracil (U), replaces thymine in RNA and differs from thymine by lacking a methyl group 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 phage|bacterial virus called PBS1 that contains uracil in its DNA. : DNA orbit animated small.gif Structure of a section of DNA. The bases lie horizontally between the two spiralling strands

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. Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson R 			 Crystal structure analysis of a complete turn of B-DNA Nature 287 			 5784 			 755-8 			 1980 			 PMID 7432492 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 transcription factor 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. Pabo C, Sauer R 			 Protein-DNA recognition Annu Rev Biochem 53 			 293-321 			PMID 6236744

 GC_Watson_Crick_basepair.png 230px AT_Watson_Crick_basepair.png,/filename> 230px  Base pair Each type of base on one strand forms a bond with just one type of base on the other strand. This is called complementary base pair ing. Here, purines form hydrogen bond 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 force s generated by the hydrophobic effect and pi stacking, but these forces are not affected by the sequence of the DNA. As hydrogen bonds are not covalent bond|covalent, 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 temperature. 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. 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. Parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in bacterial promoter s, tend to have sequences with a high AT content, making the strands easier to pull apart. In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their melting temperature (also called Tm 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. The base pairing, or lack of it, can create various topologies at the DNA end. These can be exploited in biotechnology.  Sense (molecular biology)

DNA is copied into RNA by RNA polymerase enzymes that only work in the 5' to 3' direction. 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. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmid s and virus es, blur the distinction made above between sense and antisense strands by having overlapping genes. 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 bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome. Another way of reducing genome size is seen in some viruses that contain linear or circular single-stranded DNA as their genetic material.

 DNA supercoil DNA can be twisted like a rope in a process called DNA supercoil 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. 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 topoisomerase s. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription (genetics)|transcription and DNA replication. Image:A-DNA, B-DNA and Z-DNA.png|thumb|right|290px|From left to right, the structures of A, B and Z DNA  Mechanical properties of DNA DNA exists in several possible conformations. The conformations so far identified are: A-DNA, B-DNA, C-DNA, D-DNA, E-DNA, H-DNA, L-DNA, and Z-DNA. 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 metal ion s and polyamine s. 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. Segments of DNA where the bases have been methylation|methylated may undergo a larger change in conformation and adopt the Z-DNA|Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. Image:Telomere quadruplex.jpg|thumb|left|300px|Structure of a DNA quadruplex formed by telomere repeats. <section id="6" title="Quadruplex structures"> At the ends of the linear chromosome s are specialized regions of DNA called telomere s. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as normal DNA polymerase s working on the lagging strand cannot copy the extreme 3' ends of their DNA templates. 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 exonuclease s and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence. 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. These structures are often stabilized by chelation 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 potassium ions. 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. 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. <section id="7" title="Chemical modifications"> <section id="8" title="Regulatory base modifications"> DNA methylation The expression of genes is influenced by modifications of the bases in DNA. In humans, the most common base modification is cytosine methylation to produce 5-Methylcytosine|5-methylcytosine. This modification reduces gene expression and is important in X-inactivation|X-chromosome inactivation. The level of methylation varies between organisms, with Caenorhabditis elegans lacking cytosine methylation, while vertebrate s show high levels, with up to 1% of their DNA being 5-methylcytosine. Unfortunately, the spontaneous deamination of 5-methylcytosine produces thymine, and methylated cytosines are therefore mutation hotspots. Other base modifications include adenine methylation in bacteria and the glycosylation of uracil to produce the "J-base" in kinetoplastid s	 Ratel D, Ravanat J, Berger F, Wion D 	 N6-methyladenine: the other methylated base of DNA Bioessays 28 	 3  	 309-15  	 2006  	PMID 16479578</id> Gommers-Ampt J, Van Leeuwen F, de Beer A, Vliegenthart J, Dizdaroglu M, Kowalak J, Crain P, Borst P beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei Cell 75 	 6 	 1129-36 	 1993 	PMID 8261512</id>

<section id="9" title="DNA damage"> <template type="further| Mutation " />

<link type="Image"> Benzopyrene DNA adduct 1JDG.png  250px  Benzopyrene , the major mutagen in tobacco smoking|tobacco smoke , in an adduct to DNA. DNA can be damaged by many different sorts of mutagen s. These include oxidizing agent s, alkylating agent s and also high-energy electromagnetic radiation such as ultraviolet light and x-ray s. The type of DNA damage produced depends on the type of mutagen. For example, UV light mostly damages DNA by producing thymine dimer s, which are cross-links between adjacent pyrimidine bases in a DNA strand. On the other hand, oxidants such as free radical s or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, as well as double-strand breaks. It has been estimated that in each human cell, about 500 bases suffer oxidative damage per day. Of these oxidative lesions, the most dangerous are double-strand breaks, as they can produce point mutation s, insertions and deletions from the DNA sequence, as well as chromosomal translocation s.

Many mutagens intercalation (chemistry)|intercalate into the space between two adjacent base pairs. These molecules are mostly polycyclic, aromaticity|aromatic, and planar molecules, and include ethidium , proflavin , daunomycin , doxorubicin and thalidomide. DNA intercalators are used in chemotherapy to inhibit DNA replication in rapidly-growing cancer cells. 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 transcription (genetics)|transcription and DNA replication|replication processes, causing both toxicity and mutations. As a result, DNA intercalators are often carcinogen s, with benzopyrene|benzopyrene diol epoxide, acridine s, aflatoxin and ethidium bromide being well-known examples.

==Overview of biological functions== DNA contains the genetic information that allows living things to function, grow and reproduce. This information is held in the DNA sequence|sequence of pieces of DNA called gene 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. Image:RNA pol.jpg|thumb|left|300px| T7 RNA polymerase producing a mRNA (green) from a DNA template (red and blue). The protein is shown as a purple ribbon. ===Transcription and translation=== <template type="further| Genetic code, Transcription (genetics) , Protein biosynthesis " /> A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence which then defines a protein sequence. The relationship between the nucleotide sequences of genes and the amino acid|amino-acid sequences of proteins is determined by the rules of translation (genetics)|translation, known collectively as the genetic code. 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 RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons ($$4^3$$ combinations). These encode the twenty list of standard amino acids|standard amino acids. 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.

Image:Dnareplication.png|frame|DNA replication. The double helix (blue) is unwound by a helicase. Next, DNA polymerase III (green) produces the leading strand copy (red). A DNA polymerase I molecule (green) binds to the lagging strand. This enzyme makes discontinuous segments (called Okazaki fragment s) before DNA ligase (violet) joins them together.

===Replication=== <template type="further| DNA replication " />

Cell division 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 DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. 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. 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| Cell nucleus, Gene , Non-coding DNA " /> DNA is located in the cell nucleus of eukaryotes, as well as small amounts in mitochondrion|mitochondria and chloroplast s. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The DNA is usually in linear chromosome s in eukaryotes, and circular chromosomes in prokaryotes. In the human genome, there is approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The genetic information in a genome is held within genes. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, as well as regulatory sequence s such as promoter s and enhancer (genetics)|enhancers, which control the expression of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exon s, with over 50% of human DNA consisting of non-coding repeated sequence (DNA)|repetitive sequences. The reasons for the presence of so much noncoding DNA|non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value , among species represent a long-standing puzzle known as the " C-value enigma ".

Some non-coding DNA sequences play structural roles in chromosomes. Telomere s and centromere s typically contain few genes, but are important for the function and stability of chromosomes. An abundant form of non-coding DNA in humans are pseudogene s, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossil s, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergent evolution|divergence.

==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=== Interaction of DNA with histone s (shown in white, top). These proteins' basic amino acids (below left, blue) bind to the acidic phosphate groups on DNA (below right, red).

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 chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histone s, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, 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 ionic bond s to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factor s and changing the rate of transcription. Other non-specific DNA-binding proteins found in chromatin include the high-mobility group proteins, which bind preferentially to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into more complex chromatin structures.

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. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem loop s or being degraded by nuclease s.

Image:Lambda repressor 1LMB.png|thumb|right|185px|The lambda repressor helix-turn-helix transcription factor bound to its DNA target In contrast, other proteins have evolved to specifically bind particular DNA sequences. The most intensively studied of these are the various classes of transcription factor 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 promoter 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. Alternatively, transcription factors can bind enzyme s that modify the histones at the promoter; this will change the accessibility of the DNA template to the polymerase.

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. Consequently, these proteins are often the targets of the signal transduction 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.

Image:EcoRV 1RVA.png|thumb|left|250px|The restriction enzyme EcoRV (green) in a complex with its substrate DNA

===DNA-modifying enzymes=== ====Nucleases and ligases==== Nucleases are enzyme s that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bond s. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonuclease s, while endonuclease s cut within strands. The most frequently-used nucleases in molecular biology are the restriction enzyme|restriction endonucleases, 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 bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. In technology, these sequence-specific nucleases are used in clone (genetics)|molecular cloning and DNA fingerprinting.

Enzymes called DNA ligase s can rejoin cut or broken DNA strands, using the energy from either adenosine triphosphate or nicotinamide adenine dinucleotide. Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.

====Topoisomerases and helicases==== Topoisomerase s are enzymes with both nuclease and ligase activity. These proteins change the amount of DNA supercoil|supercoiling 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. 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. Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.

Helicases are proteins that are a type of molecular motor. They use the chemical energy in adenosine triphosphate to break the hydrogen bonds between bases and unwind a DNA double helix into single strands. These enzymes are essential for most processes where enzymes need to access the DNA bases.

====Polymerases==== Polymerases are enzymes that synthesise polynucleotide chains from nucleoside triphosphate s. They function by adding nucleotides onto the 3' hydroxyl|hydroxyl group of the previous nucleotide in the DNA strand. As a consequence, all polymerases work in a 5' to 3' direction. In the active site 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 DNA replication, a DNA-dependent DNA polymerase make a DNA copy of a DNA sequence. Accuracy is vital in this process, so many of these polymerases have a Proofreading#Proofreading in biology|proofreading 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' exonuclease activity is activated and the incorrect base removed. In most organisms DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicase s.

RNA-dependent DNA polymerases are a specialised class of polymerases that copy the sequence of a RNA strand into DNA. They include reverse transcriptase, which is a virus|viral enzyme involved in the infection of cells by retrovirus es, and telomerase , which is required for the replication of telomere s. Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.

Transcription is carried out by a DNA-dependent RNA polymerase 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 promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator (genetics)|terminator, 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.

==Genetic recombination== Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow. <template type="further| Genetic recombination " /> 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).

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". 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 genetic recombination|recombine. Recombination is when two DNA helices break, swap a section and then rejoin. In eukaryotes this process usually occurs during meiosis, when the two sister chromatid 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 selection and can be important in the rapid evolution of new proteins. Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.

The most common form of recombination is chromosomal crossover|homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocation s and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as Cre recombinase. 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 complementarity (molecular biology)|complementary strand and annealing (biology)|anneal 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 Holliday junction. 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.

==Uses in technology== ===Forensics === <template type="further| Genetic fingerprinting " />

Forensic science|Forensic scientists can use DNA in blood, semen , skin , saliva or hair at a crime scene to identify a perpetrator. This process is called genetic fingerprinting, or more accurately, DNA profiling. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeat s and minisatellite s, are compared between people. This method is usually an extremely reliable technique for identifying a criminal. However, identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case. 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.

===Bioinformatics=== <template type="further| Bioinformatics " /> Bioinformatics involves the manipulation, searching, and data mining of DNA sequence data. The development of techniques to store and search DNA sequences have led to widely-applied advances in computer science, especially string searching algorithm s, machine learning and database theory. 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. In other applications such as text editor 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 sequence alignment aims to identify homology (biology)|homologous sequences and locate the specific mutation s that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetics|phylogenetic relationships and protein function. Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, 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 gene finding algorithms, which allow researchers to predict the presence of particular gene product s in an organism even before they have been isolated experimentally.

===DNA and computation === <template type="further| DNA computing " /> DNA was first used in computing to solve a small version of the directed Hamiltonian path problem, an NP-complete problem. DNA computing is advantageous over electronic computers in power use, space use, and efficiency, due to its ability to compute in a highly parallel fashion (see parallel computing ). A number of other problems, including simulation of various abstract machine s, the boolean satisfiability problem, and the bounded version of the travelling salesman problem , have since been analysed using DNA computing. Due to its compactness, DNA also has a theoretical role in cryptography, where in particular it allows unbreakable one-time pad s to be efficiently constructed and used.

===History and anthropology=== <template type="further| Phylogenetics and Genetic genealogy " /> 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 phylogeny. This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population genetics|population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology ; for example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.

DNA has also been used to look at modern family relationships, such as establishing family relationships between the descendants of Sally Hemings and Thomas Jefferson. 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.

==History== Image:Francis Crick.png|thumb|right| Francis Crick Image:JamesWatson.jpg|thumb| James D. Watson|James Watson in the Cavendish Laboratory at the University of Cambridge <template type="further| History of molecular biology " /> DNA was first isolated by Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".

In 1929 this discovery was followed by Phoebus Levene 's identification of the base, sugar and phosphate nucleotide unit. 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 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.

In 1943, Oswald Theodore Avery discovered that trait (biology)|traits 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 transforming principle. DNA's role in heredity was confirmed in 1953, when Alfred Hershey and Martha Chase in the Hershey-Chase experiment showed that DNA is the genetic material of the T2 phage.

Using X-ray diffraction data from Rosalind Franklin and the information that the bases were paired, James D. Watson and Francis Crick produced the first accurate model of DNA structure in 1953 in their article Molecular structure of Nucleic Acids|The Molecular structure of Nucleic Acids. Watson and Crick proposed the central dogma of molecular biology in 1957, describing how proteins are produced from cell nucleus|nucleic DNA. In 1962 Watson, Crick, and Maurice Wilkins jointly received the Nobel Prize in Nobel Prize in Physiology or Medicine|Physiology or Medicine.

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". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson-Stahl experiment. Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology.

==References==

==Further reading== Clayton, Julie. (Ed.). 50 Years of DNA, Palgrave MacMillan Press, 2003. ISBN 978-1-40-391479-8 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 Robert Olby|Olby, Robert. 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. Matt Ridley|Ridley, Matt. 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 Rose, Steven. The Chemistry of Life, Penguin, ISBN 978-0-14-027273-4. Watson, James D. and Francis H.C. Crick. A structure for Deoxyribose Nucleic Acid (PDF). Nature (journal)|Nature 171, 737 – 738, 25 April 1953. Watson, James D. DNA: The Secret of Life ISBN 978-0-375-41546-3. Watson, James D. The Double Helix|The Double Helix: A Personal Account of the Discovery of the Structure of DNA (Norton Critical Editions). ISBN 978-0-393-95075-5 ==External links== <template type="Spoken FAMEPedia|dna.ogg|2007-02-12" /> <template type="commonscat|DNA" /> *DNA from the beginning *Double helix: 50 years of DNA, Nature (journal)|Nature *Rosalind Franklin's contributions to the study of DNA *U.S. National DNA Day - watch videos and participate in real-time chat with top scientists *Genetic Education Modules for Teachers - DNA from the Beginning Study Guide *Listen to Francis Crick and James Watson talking on the BBC in 1962, 1972, and 1974 *Using DNA in Genealogical Research *DNA Interactive (requires Adobe Flash ) *DNA: RCSB PDB Molecule of the Month *DNA under electron microscope *<template type="dmoz|Science/Biology/Biochemistry_and_Molecular_Biology/Biomolecules/Nucleic_Acids/DNA/|DNA" /> *DNA Articles - articles and information collected from various sources *<template type="McGrawHillAnimation|genetics|Dna%20Replication" /> *DNA coiling to form chromosomes

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DNA Genetics

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= Stub Article in XML Format = <wikiarticle linkback="Franklin Pierce High School" revisiondate="2007-02-08T20:18:03Z"> Franklin Pierce High School Stub <infobox type="Secondary school"> name Franklin Pierce High School established 1952         city Tacoma state Washington country USA campus Suburban type Public secondary principal Eric Hogan grades 9-12         enrollment 1,220 (2005)         district Franklin Pierce School District mascot Cardinals colors Red and yellow website http://www.fp.k12.wa.us/fphs/ Franklin Pierce High School in Tacoma, Washington is named after the fourteenth US President, Franklin Pierce, who was president when the Washington Territory was formed in 1853. <section id="1" title="Academics"> Advanced Placement 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 id="2" title="Activies"> Clubs at FPHS are Drama Club, FBLA, FFA , National Honor Society , International Cultures Club, and Ski Club. <section id="3" title="Athletics"> Football, Golf, Cross Country, Volleyball, Soccer,Basketball, Wrestling, Tennis, Baseball, Fastpitch Softball, and Track. Category:High schools in Washington Category:South Puget Sound League Category:Educational institutions established in 1952 106992867         2007-02-09T20:45:00Z Quirkyperki 106992539         2007-02-09T20:43:00Z Quirkyperki (Created page with '{{Infobox Secondary school | name = Franklin Pierce High School | established = 1952 | city = Tacoma | state = Washington | country = USA | campus = Suburban | type...')

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<wikiarticle linkback="Neuralizer" revisiondate="2007-01-01T16:28:49Z"> Neuralizer <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.