Editing G2 phase (section)

== G2/M DNA damage arrest ==
{{see also|DNA damage checkpoint|}}Cells respond to [[DNA damage (naturally occurring)|DNA damage]] or incompletely replicated chromosomes in G2 phase by delaying the G2/M transition so as to prevent attempts to segregate damaged chromosomes. DNA damage is detected by the kinases [[ATM serine/threonine kinase|ATM]] and [[Ataxia telangiectasia and Rad3 related|ATR]], which activate [[CHEK1|Chk1]], an inhibitory kinase of Cdc25. Chk1 inhibits Cdc25 activity both directly and by promoting its exclusion from the nucleus.<ref name=":0" /> The net effect is an increase in the threshold of cyclin B1 required to initiate the hysteretic transition to M-phase, effectively stalling the cell in G2 until the damage is repaired by mechanisms such as homology-directed repair (see above).<ref name="Sible 2003" /> 

Long-term maintenance of the G2 arrest is also mediated by [[p53]], which is stabilized in response to DNA damage. CDK1 is directly inhibited by three transcriptional targets of p53: [[p21]], [[Gadd45]], and [[14-3-3σ]]. Inactive Cyclin B1/CDK1 is sequestered in the nucleus by p21,<ref name="Dulic 2004">{{cite journal | vauthors = Charrier-Savournin FB, Château MT, Gire V, Sedivy J, Piette J, Dulic V | title = p21-Mediated nuclear retention of cyclin B1-Cdk1 in response to genotoxic stress | journal = Molecular Biology of the Cell | volume = 15 | issue = 9 | pages = 3965–76 | date = September 2004 | pmid = 15181148 | pmc = 515331 | doi = 10.1091/mbc.E03-12-0871 }}</ref> while active Cyclin B1/CDK1 complexes are sequestered in the cytoplasm by 14-3-3σ.<ref name="stark 2001">{{cite journal | vauthors = Taylor WR, Stark GR | title = Regulation of the G2/M transition by p53 | journal = Oncogene | volume = 20 | issue = 15 | pages = 1803–15 | date = April 2001 | pmid = 11313928 | doi = 10.1038/sj.onc.1204252 | s2cid = 9543421 | doi-access =  }}</ref> Gadd45 disrupts the binding of Cyclin B1 and CDK1 through direct interaction with CDK1. P53 also directly transcriptionally represses CDK1.<ref name="stark 2001" /><ref>{{cite journal | vauthors = Innocente SA, Abrahamson JL, Cogswell JP, Lee JM | title = p53 regulates a G2 checkpoint through cyclin B1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 5 | pages = 2147–52 | date = March 1999 | pmid = 10051609 | pmc = 26751 | doi = 10.1073/pnas.96.5.2147 | bibcode = 1999PNAS...96.2147I | doi-access = free }}</ref>