Article
- The EMBO Journal (2006) 25, 1285 - 1294
- doi:10.1038/sj.emboj.7600993
Published online: 16 February 2006
Subject Category:
DNA interstrand crosslink repair during G1 involves nucleotide excision repair and DNA polymerase 
Sovan Sarkar1, Adelina A Davies2, Helle D Ulrich2 and Peter J McHugh1
- Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
- Cancer Research UK London Research Institute, Clare Hall Laboratories, Potters Bar, Herts, UK
Correspondence to:
Peter J McHugh, Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK. Tel.: +44 1865 222 441; Fax: +44 1865 222 431; E-mail: peter.mchugh@cancer.org.uk
Received 7 December 2005; Accepted 17 January 2006; Revised 11 January 2006
Abstract
The repair mechanisms acting on DNA interstrand crosslinks (ICLs) in eukaryotes are poorly understood. Here, we provide evidence for a pathway of ICL processing that uses components from both nucleotide excision repair (NER) and translesion synthesis (TLS) and predominates during the G1 phase of the yeast cell cycle. Our results suggest that repair is initiated by the NER apparatus and is followed by a thwarted attempt at gap-filling by the replicative Polymerase 
, which likely stalls at the site of the remaining crosslinked oligonucleotide. This in turn leads to ubiquitination of PCNA and recruitment of the damage-tolerant Polymerase 
that can perform TLS. The ICL repair factor Pso2 acts downstream of the incision step and is not required for Polymerase activation. We show that this combination of NER and TLS is the only pathway of ICL repair available to the cell in G1 phase and is essential for viability in the presence of DNA crosslinks.
Keywords:
- DNA interstrand crosslinks,
- nucleotide excision repair,
- PCNA,
- translesion synthesis
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