What ensures that DNA damage is repaired before mitosis?
Faithful genome transmission requires that DNA lesions incurred during replication or from external mutagens be repaired before chromosomes condense and segregate to avoid transmitting broken chromosomes and rearrangements. G2/M checkpoint serves this function by integrating damage sensing with CDK1 control. Lesions such as double-strand breaks recruit MRN complex MRE11-RAD50-NBS1 that activates ATM kinase, while RPA-coated single-stranded DNA from resection or stalled forks recruits ATRIP-ATR and TopBP1 activator. Effector kinases Chk2 and Chk1 phosphorylate dual-specificity phosphatases Cdc2
Ref: Sancar et al., Annu Rev Biochem 2004, DNA Repair Checkpoints. Alberts 7th ed., Chapter 17, G2/M Damage Control.
