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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{dagger}

Takashi Okada ,1,2,{ddagger},§ Eiichiro Sonoda,1,{ddagger} Michio Yoshimura,1,3 Yoshiaki Kawano,4 Hideyuki Saya,4 Masaoki Kohzaki,1,5 and Shunichi Takeda1*

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{zeta} (Rev3-Rev7)-independent role of Rev1 in vertebrate cells.

* Corresponding author. Mailing address: Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan. Phone: 81-75-753-4410. Fax: 81-75-753-4419. E-mail: stakeda{at}rg.med.kyoto-u.ac.jp.

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

{ddagger} T.O. and E.S. contributed equally to this work.

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

Molecular and Cellular Biology, July 2005, p. 6103-6111, Vol. 25, No. 14
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.14.6103-6111.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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