Editing DNA sequencing (section)

== The four canonical bases ==
{{Main|Nucleotide}}
The canonical structure of DNA has four bases: [[thymine]] (T), [[adenine]] (A), [[cytosine]] (C), and [[guanine]] (G). DNA sequencing is the determination of the physical order of these bases in a molecule of DNA. However, there are many other bases that may be present in a molecule. In some viruses (specifically, [[bacteriophage]]), cytosine may be replaced by hydroxy methyl or hydroxy methyl glucose cytosine.<ref>{{cite journal | vauthors = Moréra S, Larivière L, Kurzeck J, Aschke-Sonnenborn U, Freemont PS, Janin J, Rüger W | title = High resolution crystal structures of T4 phage beta-glucosyltransferase: induced fit and effect of substrate and metal binding | journal = Journal of Molecular Biology | volume = 311 | issue = 3 | pages = 569–77 | date = August 2001 | pmid = 11493010 | doi = 10.1006/jmbi.2001.4905 }}</ref> In mammalian DNA, variant bases with [[methyl]] groups or phosphosulfate may be found.<ref>{{cite journal | vauthors = Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, Gehrke C | title = Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells | journal = Nucleic Acids Research | volume = 10 | issue = 8 | pages = 2709–21 | date = April 1982 | pmid = 7079182 | pmc = 320645 | doi = 10.1093/nar/10.8.2709 }}</ref><ref>{{cite journal | vauthors = Ehrlich M, Wang RY | title = 5-Methylcytosine in eukaryotic DNA | journal = Science | volume = 212 | issue = 4501 | pages = 1350–7 | date = June 1981 | pmid = 6262918 | doi = 10.1126/science.6262918 | bibcode = 1981Sci...212.1350E }}</ref> Depending on the sequencing technique, a particular modification, e.g., the 5mC ([[5-Methylcytosine]]) common in humans, may or may not be detected.<ref>{{cite journal | vauthors = Song CX, Clark TA, Lu XY, Kislyuk A, Dai Q, Turner SW, He C, Korlach J | display-authors = 6 | title = Sensitive and specific single-molecule sequencing of 5-hydroxymethylcytosine | journal = Nature Methods | volume = 9 | issue = 1 | pages = 75–7 | date = November 2011 | pmid = 22101853 | pmc = 3646335 | doi = 10.1038/nmeth.1779 }}</ref>

In almost all organisms, DNA is synthesized in vivo using only the 4 canonical bases; modification that occurs post replication creates other bases like 5 methyl C. However, some bacteriophage can incorporate a non standard base directly.<ref>{{cite journal |last1=Czernecki |first1=Dariusz |last2=Bonhomme |first2=Frédéric |last3=Kaminski |first3=Pierre-Alexandre |last4=Delarue |first4=Marc |title=Characterization of a triad of genes in cyanophage S-2L sufficient to replace adenine by 2-aminoadenine in bacterial DNA |journal=Nature Communications |date=5 August 2021 |volume=12 |issue=1 |pages=4710 |doi=10.1038/s41467-021-25064-x |pmid=34354070 |bibcode=2021NatCo..12.4710C |s2cid=233745192 |doi-access=free |pmc=8342488 }}</ref>

In addition to modifications, DNA is under constant assault by environmental agents such as UV and Oxygen radicals. At the present time, the presence of such damaged bases is not detected by most DNA sequencing methods, although PacBio has published on this.<ref>{{Cite web |title=Direct detection and sequencing of damaged DNA bases. |url=https://www.pacb.com/publications/direct-detection-and-sequencing-of-damaged-dna-bases/ |access-date=2024-07-31 |website=PacBio |language=en-US}}</ref>