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Multiple roles of Rev3, the catalytic subunit of polζ in maintaining genome stability in vertebrates
Author(s) -
Sonoda Eiichiro,
Okada Takashi,
Zhao Guang Yu,
Tateishi Satoshi,
Araki Kasumi,
Yamaizumi Masaru,
Yagi Takashi,
Verkaik Nicole S.,
van Gent Dik C.,
Takata Minoru,
Takeda Shunichi
Publication year - 2003
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 - 10.1093/emboj/cdg308
Subject(s) - biology , homologous recombination , dna repair , dna damage , dna , gene , dna replication , microbiology and biotechnology , dna polymerase , plasmid , non homologous end joining , genetics
Translesion DNA synthesis (TLS) and homologous DNA recombination (HR) are two major postreplicational repair (PRR) pathways. The REV3 gene of Saccharomyces cerevisiae encodes the catalytic subunit of DNA polymerase ζ, which is involved in mutagenic TLS. To investigate the role of REV3 in vertebrates, we disruped the gene in chicken DT40 cells. REV3 −/− cells are sensitive to various DNA‐damaging agents, including UV, methyl methanesulphonate (MMS), cisplatin and ionizing radiation (IR), consistent with its role in TLS. Interestingly, REV3 −/− cells showed reduced gene targeting efficiencies and significant increase in the level of chromosomal breaks in the subsequent M phase after IR in the G 2 phase, suggesting the involvement of Rev3 in HR‐mediated double‐strand break repair. REV3 −/− cells showed significant increase in sister chromatid exchange events and chromosomal breaks even in the absence of exogenous genotoxic stress. Furthermore, double mutants of REV3 and RAD54 , genes involved in HR, are synthetic lethal. In conclusion, Rev3 plays critical roles in PRR, which accounts for survival on naturally occurring endogenous as well as induced damages during replication.