The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair.
The Fanconi anemia (FA) protein FANCC is essential for chromosome stability in vertebrate cells, a feature underscored by the extreme sensitivity of FANCC-deficient cells to agents that crosslink DNA. However, it is not known how this FA protein facilitates the repair of both endogenously acquired and mutagen-induced DNA damage. Here, we use the model vertebrate cell line DT40 to address this question. We discover that apart from functioning in homologous recombination, FANCC also promotes the mutational repair of endogenously generated abasic sites. Moreover in these vertebrate cells, the efficient repair of crosslinks requires the combined functions of FANCC, translesion synthesis, and homologous recombination. These studies reveal that the FA proteins cooperate with key mutagenesis and repair processes that enable replication of damaged DNA.
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom.
Wojciech
W
Niedzwiedz
Georgina
G
Mosedale
Mark
M
Johnson
Chong Yi
CY
Ong
Paul
P
Pace
Ketan J
KJ
Patel
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D002645:Chickens; D043171:Chromosomal Instability; D003432:Cross-Linking Reagents / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004843:Epistasis, Genetic; D005199:Fanconi Anemia; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D014965:X-Rays; D000099270:Y-Family DNA Polymerases
D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D004247:DNA; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D011506:Proteins; D011993:Recombinant Fusion Proteins; C497651:FANCC protein, human; C499905:FANCD2 protein, human; C429004:REV1 protein, human; D000099270:Y-Family DNA Polymerases; C118285:REV3L protein, human