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DNA interstrand crosslink repair during G1 involves nucleotide excision repair and DNA polymerase ζ
Author(s) -
Sarkar Sovan,
Davies Adelina A,
Ulrich Helle D,
McHugh Peter J
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600993
Subject(s) - nucleotide excision repair , proliferating cell nuclear antigen , dna repair , dna polymerase , dna polymerase delta , polymerase , dna damage , microbiology and biotechnology , dna , biology , chemistry , oligonucleotide , genetics , gene , polymerase chain reaction , reverse transcriptase
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 δ, 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 ζ that can perform TLS. The ICL repair factor Pso2 acts downstream of the incision step and is not required for Polymerase ζ 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.