Which checkpoint kinase ensures DNA integrity before mitosis?
Genome surveillance employs two parallel transducer kinases converging on cell cycle arrest before mitosis. ATR-Chk1 pathway responds primarily to single-stranded DNA, stalled forks, base adducts and resected double-strand break ends processed by Exo1 and CtIP nucleases. ATM-Chk2 pathway recognizes blunt double-strand breaks via MRN complex Mre11-Rad50-Nbs1 mediated ATM recruitment and activation at break sites. Activated ATR phosphorylates Chk1, while ATM phosphorylates Chk2 at Thr68 promoting dimerization and full activation through autophosphorylation at Thr383 Thr387 in activation loop. Bo
Ref: Bartek & Lukas, Chk1 and Chk2 checkpoint kinases, Cancer Cell 2003; NCBI Bookshelf, G2/M DNA Damage Checkpoint.
