title: Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM.
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 approximately 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.
authors.affiliation: Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Hirano
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ishiai
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yamazoe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
authors.forename: Nobuko
authors.initials: N
authors.lastname: Matsushita
authors.forename: Mioko
authors.initials: M
authors.lastname: Ohzeki
authors.forename: Yukiko M
authors.initials: YM
authors.lastname: Yamashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arakawa
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Buerstedde
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Larry H
authors.initials: LH
authors.lastname: Thompson
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D030161:Avian Proteins; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000502:physiology*; D002460:Cell Line; D004265:DNA Helicases / Q000502:physiology*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology*; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000502:physiology*; D051135:Rad51 Recombinase; D053484:RecQ Helicases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012854:Sister Chromatid Exchange; D044767:Ubiquitin-Protein Ligases
chemical_list: D030161:Avian Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; C485954:RAD18 protein, human; D011993:Recombinant Fusion Proteins; C110901:X-ray repair cross complementing protein 3; D049452:Green Fluorescent Proteins; D044767:Ubiquitin-Protein Ligases; C495150:RAD51 protein, Gallus gallus; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases