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Molecular and Cellular Biology, July 2005, p. 6103-6111, Vol. 25, No. 14
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.14.6103-6111.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Multiple Roles of Vertebrate REV Genes in DNA Repair and Recombination

Takashi Okada ,^1,2,, Eiichiro Sonoda,^1, Michio Yoshimura,^1,3 Yoshiaki Kawano,⁴ Hideyuki Saya,⁴ Masaoki Kohzaki,^1,5 and Shunichi Takeda^1*

Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan,¹ Departments of Urology,² Therapeutic Radiology & Oncology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan,³ Department of Oncology, Kumamoto University School of Medicine, Kumamoto 862-0811, Japan,⁴ Department of Radiology and Radiation Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8521, Japan⁵

Received 8 September 2004/ Returned for modification 24 November 2004/ Accepted 5 April 2005

In yeast, Rev1, Rev3, and Rev7 are involved in translesion synthesis over various kinds of DNA damage and spontaneous and UV-induced mutagenesis. Here, we disrupted Rev1, Rev3, and Rev7 in the chicken B-lymphocyte line DT40. REV1^–/– REV3^–/– REV7^–/– cells showed spontaneous cell death, chromosomal instability/fragility, and hypersensitivity to various genotoxic treatments as observed in each of the single mutants. Surprisingly, the triple-knockout cells showed a suppressed level of sister chromatid exchanges (SCEs), which may reflect postreplication repair events mediated by homologous recombination, while each single mutant showed an elevated SCE level. Furthermore, REV1^–/– cells as well as triple mutants showed a decreased level of immunoglobulin gene conversion, suggesting participation of Rev1 in a recombination-based pathway. The present study gives us a new insight into cooperative function of three Rev molecules and the Pol (Rev3-Rev7)-independent role of Rev1 in vertebrate cells.

Supplemental material for this article may be found at http://mcb.asm.org/.

T.O. and E.S. contributed equally to this work.

Present address: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

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