CHEK1 is recruited to resected DNA DSBs

Stable Identifier
Homo sapiens
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The recruitment of CHEK1 (CHK1) to resected DNA double strand breaks (DSBs) and activation by ATR-mediated phosphorylation requires the presence of CLSPN (claspin) and TIMELESS:TIPIN protein complex. TIPIN simultaneously interacts with the RPA2 subunit of the RPA complex and CLSPN, allowing CLSPN to stably associate with resected DNA DSBs (Kemp et al. 2010). Phosphorylation of CLSPN at threonine T916 and serine S945 is needed for CHEK1 binding (Kumagai et al. 2003, Clarke and Clarke 2005). CLSPN phosphorylation at these sites is independent of CHEK1 (Bennett et al. 2008). Casein kinase 1 (CK1) was proposed as a kinase responsible for CLSPN phosphorylation (Meng et al. 2011) but the exact mechanism of this modification has not been established.

ATR-mediated phosphorylation of RAD17 on serine residues S635 and S645 is implicated in CLSPN recruitment to resected DNA DSBs and CLSPN phosphorylation (Wang et al. 2006). Also, phosphorylation of the RPA2 subunit of the RPA complex positively contributes to CHEK1 activation (Liu et al. 2012).

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Orthologous Events