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. Author manuscript; available in PMC: 2016 Jan 1.
Published in final edited form as: Mutat Res Rev Mutat Res. 2014 Oct 22;763:168–180. doi: 10.1016/j.mrrev.2014.10.003

Figure 3. Chk1 functions in DNA replication.

Figure 3

A nucleus in S phase with replication factories foci is shown. The arrow represents the incidence of DNA damage upon a given factory. Note that in unperturbed conditions endogenous damage can account for Chk1 activation. Active Chk1 performs its function at the same replication fork that activates it (in cis) or, after being released to the nucleoplasm, at other replication factories (in trans).

In trans Chk1 inhibits origin firing by preventing Cdc45 loading. In unperturbed conditions this is achieved by Chk1-dependent Cdc25A degradation. Upon genotoxic stress, apart from impinging on Cdk2 activity, Chk1 might also inactivate Cdc7 and disrupt the interaction between TopBP1 and treslin; both mechanisms lead to impaired loading of the Cdc45-MCM2-7-GINS replicative helicase.

In cis Chk1 prevents DSB formation by unknown mechanisms, thereby stabilizing forks. Chk1 also aids HR repair of collapsed forks by positively regulating the recruitment of Rad51 and limits genomic instability by restraining the activity of Mus81 and other nucleases. In addition, Chk1 might promote the elongation of forks that have stalled and allow dormant origin firing to ensure that DNA replication is completed (not represented).