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PMID: 12805232 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Multiple roles of Rev3, the catalytic subunit of polzeta in maintaining genome stability in vertebrates.

The EMBO journal ·Vol. 22 ·No. 12 ·2003-06-16 ·Pages 3188-97

Sonoda E, Okada T, Zhao GY, Tateishi S, Araki K, Yamaizumi M, Yagi T, Verkaik NS, van Gent DC, Takata M, Takeda S

Abstract

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 zeta, 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.

MeSH Terms
Animals Catalytic Domain Cell Line Chickens Chromosome Aberrations DNA/genetics,metabolism,radiation effects DNA Damage DNA Helicases DNA Repair DNA Repair Enzymes DNA Replication/physiology DNA-Directed DNA Polymerase/chemistry,genetics,metabolism Genome Mutation Radiation, Ionizing Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/chemistry,genetics,metabolism Sister Chromatid Exchange
Chemicals
Saccharomyces cerevisiae Proteins DNA DNA polymerase zeta DNA-Directed DNA Polymerase REV3 protein, S cerevisiae RAD54 protein, S cerevisiae DNA Helicases DNA Repair Enzymes
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Sonoda Eiichiro
CREST Research Project, Japan Science and Technology, Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
Okada Takashi
Zhao Guang Yu
Tateishi Satoshi
Araki Kasumi
Yamaizumi Masaru
Yagi Takashi
Verkaik Nicole S
van Gent Dik C
Takata Minoru
Takeda Shunichi
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg308
Published
2003-06-16
Pages
3188-97
Language
English
Region
England
NLM ID
8208664
PMCID
PMC162160
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg308 PMC Full Text View journal details
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