The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair

被引:256
作者
Niedzwiedz, W
Mosedale, G
Johnson, M
Ong, CY
Pace, P
Patel, KJ
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
[2] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2SP, England
基金
英国医学研究理事会;
关键词
D O I
10.1016/j.molcel.2004.08.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:607 / 620
页数:14
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