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Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM
Author(s) -
Hirano Seiki,
Yamamoto Kazuhiko,
Ishiai Masamichi,
Yamazoe Mitsuyoshi,
Seki Masayuki,
Matsushita Nobuko,
Ohzeki Mioko,
Yamashita Yukiko M,
Arakawa Hiroshi,
Buerstedde JeanMarie,
Enomoto Takemi,
Takeda Shunichi,
Thompson Larry H,
Takata Minoru
Publication year - 2005
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 - 10.1038/sj.emboj.7600534
Subject(s) - biology , homologous recombination , homologous chromosome , genetics , recombination , microbiology and biotechnology , dna , gene
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.