Article
- The EMBO Journal (2005) 24, 418 - 427
- doi:10.1038/sj.emboj.7600534
Published online: 23 December 2004
Subject Category:
Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM
Seiki Hirano1, Kazuhiko Yamamoto1,a, Masamichi Ishiai1, Mitsuyoshi Yamazoe2, Masayuki Seki3, Nobuko Matsushita1, Mioko Ohzeki1, Yukiko M Yamashita2, Hiroshi Arakawa4, Jean-Marie Buerstedde4, Takemi Enomoto3, Shunichi Takeda2, Larry H Thompson5 and Minoru Takata1
- Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki, Okayama, Japan
- Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-konoe, Sakyo-ku, Kyoto, Japan
- Molecular Cell Biology Laboratory, Graduate School for Pharmaceutical Sciences, Tohoku University, Aoba, Aoba-ku, Sendai, Miyagi, Japan
- GSF, Institute for Molecular Radiobiology, Neuherberg Munich, Germany
- Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA, USA
Correspondence to:
Minoru Takata, Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. Tel.: +81 86 462 1111; Fax: +81 86 464 1187; E-mail: mtakata@med.kawasaki-m.ac.jp
aPresent address: Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA
Received 24 June 2004; Accepted 6 December 2004
Abstract
Some of the restarting events of stalled replication forks lead to sister chromatid exchange (SCE) as a result of homologous recombination (HR) repair with crossing over. The rate of SCE is elevated by the loss of BLM helicase or by a defect in translesion synthesis (TLS). We found that spontaneous SCE levels were elevated 
2-fold in chicken DT40 cells deficient in Fanconi anemia (FA) gene FANCC. To investigate the mechanism of the elevated SCE, we deleted FANCC in cells lacking Rad51 paralog XRCC3, TLS factor RAD18, or BLM. The increased SCE in fancc cells required Xrcc3, whereas the fancc/rad18 double mutant exhibited higher SCE than either single mutant. Unexpectedly, SCE in the fancc/blm mutant was similar to that in blm cells, indicating functional linkage between FANCC and BLM. Furthermore, MMC-induced formation of GFP-BLM nuclear foci was severely compromised in both human and chicken fancc or fancd2 cells. Our cell survival data suggest that the FA proteins serve to facilitate HR, but not global TLS, during crosslink repair.
Keywords:
- Bloom syndrome,
- Fanconi anemia,
- homologous recombination,
- sister chromatid exchange,
- translesion synthesis
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