Editing Origin of replication (section)

== Features ==
A key prerequisite for DNA replication is that it must occur with extremely high fidelity and efficiency exactly once per [[cell cycle]] to prevent the accumulation of genetic alterations with potentially deleterious consequences for cell survival and organismal viability.<ref>{{cite journal | vauthors = O'Donnell M, Langston L, Stillman B | title = Principles and concepts of DNA replication in bacteria, archaea, and eukarya | journal = Cold Spring Harbor Perspectives in Biology | volume = 5 | issue = 7 | pages = a010108 | date = July 2013 | pmid = 23818497 | pmc = 3685895 | doi = 10.1101/cshperspect.a010108 }}</ref> Incomplete, erroneous, or untimely DNA replication events can give rise to mutations, chromosomal [[polyploidy]] or [[aneuploidy]], and gene copy number variations, each of which in turn can lead to diseases, including cancer.<ref>{{cite journal | vauthors = Abbas T, Keaton MA, Dutta A | title = Genomic instability in cancer | journal = Cold Spring Harbor Perspectives in Biology | volume = 5 | issue = 3 | pages = a012914 | date = March 2013 | pmid = 23335075 | pmc = 3578360 | doi = 10.1101/cshperspect.a012914 }}</ref><ref name=":1">{{cite journal | vauthors = Barlow JH, Nussenzweig A | title = Replication initiation and genome instability: a crossroads for DNA and RNA synthesis | journal = Cellular and Molecular Life Sciences | volume = 71 | issue = 23 | pages = 4545–59 | date = December 2014 | pmid = 25238783 | pmc = 6289259 | doi = 10.1007/s00018-014-1721-1 }}</ref> To ensure complete and accurate duplication of the entire genome and the correct flow of genetic information to progeny cells, all DNA replication events are not only tightly regulated with cell cycle cues but are also coordinated with other cellular events such as [[Transcription (biology)|transcription]] and [[DNA repair]].<ref name="Ekundayo et al"/><ref>{{cite journal | vauthors = Siddiqui K, On KF, Diffley JF | title = Regulating DNA replication in eukarya | journal = Cold Spring Harbor Perspectives in Biology | volume = 5 | issue = 9 | pages = a012930 | date = September 2013 | pmid = 23838438 | pmc = 3753713 | doi = 10.1101/cshperspect.a012930 }}</ref><ref>{{cite journal | vauthors = Sclafani RA, Holzen TM | title = Cell cycle regulation of DNA replication | journal = Annual Review of Genetics | volume = 41 | pages = 237–80 | date = 2007 | pmid = 17630848 | pmc = 2292467 | doi = 10.1146/annurev.genet.41.110306.130308 }}</ref><ref name=":2">{{cite journal | vauthors = García-Muse T, Aguilera A | title = Transcription-replication conflicts: how they occur and how they are resolved | journal = Nature Reviews. Molecular Cell Biology | volume = 17 | issue = 9 | pages = 553–63 | date = September 2016 | pmid = 27435505 | doi = 10.1038/nrm.2016.88 | hdl = 11441/101680 | s2cid = 7617164 | url = https://idus.us.es/handle//11441/101680 }}</ref> Additionally, origin sequences commonly have high [[AT-content]] across all kingdoms, since repeats of adenine and thymine are easier to separate because their base stacking interactions are not as strong as those of guanine and cytosine.<ref>{{cite journal | vauthors = Yakovchuk P, Protozanova E, Frank-Kamenetskii MD | title = Base-stacking and base-pairing contributions into thermal stability of the DNA double helix | journal = Nucleic Acids Research | volume = 34 | issue = 2 | pages = 564–74 | year = 2006 | pmid = 16449200 | pmc = 1360284 | doi = 10.1093/nar/gkj454 }}</ref>

DNA replication is divided into different stages. During initiation, the replication machineries – termed [[replisome]]s – are assembled on DNA in a bidirectional fashion. These assembly loci constitute the start sites of DNA replication or replication origins. In the elongation phase, replisomes travel in opposite directions with the replication forks, unwinding the DNA helix and synthesizing complementary daughter DNA strands using both parental strands as templates. Once replication is complete, specific termination events lead to the disassembly of replisomes. As long as the entire genome is duplicated before cell division, one might assume that the location of replication start sites does not matter; yet, it has been shown that many organisms use preferred genomic regions as origins.<ref name=":15">{{cite journal | vauthors = Leonard AC, Méchali M | title = DNA replication origins | journal = Cold Spring Harbor Perspectives in Biology | volume = 5 | issue = 10 | pages = a010116 | date = October 2013 | pmid = 23838439 | pmc = 3783049 | doi = 10.1101/cshperspect.a010116 }}</ref><ref name=":16">{{cite journal | vauthors = Creager RL, Li Y, MacAlpine DM | title = SnapShot: Origins of DNA replication | journal = Cell | volume = 161 | issue = 2 | pages = 418–418.e1 | date = April 2015 | pmid = 25860614 | doi = 10.1016/j.cell.2015.03.043 | doi-access = free }}</ref> The necessity to regulate origin location likely arises from the need to coordinate DNA replication with other processes that act on the shared chromatin template to avoid DNA strand breaks and DNA damage.<ref name="Ekundayo et al"/><ref name=":1" /><ref name=":2" /><ref>{{cite journal | vauthors = Knott SR, Viggiani CJ, Aparicio OM | title = To promote and protect: coordinating DNA replication and transcription for genome stability | journal = Epigenetics | volume = 4 | issue = 6 | pages = 362–5 | date = August 2009 | pmid = 19736523 | doi = 10.4161/epi.4.6.9712 | doi-access = free }}</ref><ref name="#8638128">{{cite journal | vauthors = Deshpande AM, Newlon CS | title = DNA replication fork pause sites dependent on transcription | journal = Science | volume = 272 | issue = 5264 | pages = 1030–3 | date = May 1996 | pmid = 8638128 | doi = 10.1126/science.272.5264.1030 | bibcode = 1996Sci...272.1030D | s2cid = 38817771 }}</ref><ref name="#27362223"/><ref>{{cite journal | vauthors = Liu B, Alberts BM | title = Head-on collision between a DNA replication apparatus and RNA polymerase transcription complex | journal = Science | volume = 267 | issue = 5201 | pages = 1131–7 | date = February 1995 | pmid = 7855590 | doi = 10.1126/science.7855590 | bibcode = 1995Sci...267.1131L | s2cid = 6835136 }}</ref><ref>{{cite journal | vauthors = Azvolinsky A, Giresi PG, Lieb JD, Zakian VA | title = Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae | journal = Molecular Cell | volume = 34 | issue = 6 | pages = 722–34 | date = June 2009 | pmid = 19560424 | pmc = 2728070 | doi = 10.1016/j.molcel.2009.05.022 }}</ref>