Title: Replication protein A safeguards genome integrity by controlling NER incision events.

Authors: Overmeer, René M; Moser, Jill; Volker, Marcel; Kool, Hanneke; Tomkinson, Alan E; van Zeeland, Albert A; Mullenders, Leon H F; Fousteri, Maria

Published In J Cell Biol, (2011 Feb 07)

Abstract: Single-stranded DNA gaps that might arise by futile repair processes can lead to mutagenic events and challenge genome integrity. Nucleotide excision repair (NER) is an evolutionarily conserved repair mechanism, essential for removal of helix-distorting DNA lesions. In the currently prevailing model, NER operates through coordinated assembly of repair factors into pre- and post-incision complexes; however, its regulation in vivo is poorly understood. Notably, the transition from dual incision to repair synthesis should be rigidly synchronized as it might lead to accumulation of unprocessed repair intermediates. We monitored NER regulatory events in vivo using sequential UV irradiations. Under conditions that allow incision yet prevent completion of repair synthesis or ligation, preincision factors can reassociate with new damage sites. In contrast, replication protein A remains at the incomplete NER sites and regulates a feedback loop from completion of DNA repair synthesis to subsequent damage recognition, independently of ATR signaling. Our data reveal an important function for replication protein A in averting further generation of DNA strand breaks that could lead to mutagenic and recombinogenic events.

PubMed ID: 21282463

MeSH Terms: No MeSH terms associated with this publication