Reaction: Activation of CHEK1 at resected DNA DSBs
- in pathway: Processing of DNA double-strand break ends
CHEK1 (Chk1) is a checkpoint kinase activated during genotoxic stress. CHEK1 activation at resected DNA double-strand breaks (DSBs) involves ATR-mediated phosphorylation of CHEK1 serine residues S317 and S345 in the presence of claspin (CLSPN), TOPBP1, RAD17:RFC complex, RAD9:HUS1:RAD1 complex, TIMELESS:TIPIN complex, RPA complex and RHNO1 (Liu et al. 2000, Zhao and Piwnica-Worms 2001, Kumagai and Dunphy 2003, Sorensen et al. 2004, Wang et al. 2006, Kemp et al. 2010, Cotta-Ramusino et al. 2011, Liu et al. 2012). Following phosphorylation, CHEK1 dissociates from chromatin and phosphorylates target proteins involved in S/G2 checkpoint activation and/or homologous recombination repair (Smits et al. 2006). CLSPN needs to interact with chromatin only transiently in order to facilitate CHEK1 activation (Lee et al. 2005).
Reaction - small molecule participants:
ADP [nucleoplasm]
ATP [nucleoplasm]
Reactome.org reaction link: R-HSA-5684887
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Reaction input - small molecules:
ATP(4-)
Reaction output - small molecules:
ADP(3-)
Reactome.org link: R-HSA-5684887