XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair

被引：540
作者：
Whitehouse, CJ
Taylor, RM
Thistlethwaite, A
Zhang, H
Karimi-Busheri, F
Lasko, DD
Weinfeld, M
Caldecott, KW
机构：
[1] Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England
[2] Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB T6G 1Z2, Canada
[3] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Mol Oncol Grp, Montreal, PQ H3T 1E2, Canada
来源：
CELL | 2001年 / 104卷 / 01期
基金：
英国医学研究理事会;
关键词：
D O I：
10.1016/S0092-8674(01)00195-7
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：
XRCC1 protein is required for DNA single-strand break repair and genetic stability but its biochemical role is unknown. Here, we report that XRCC1 interacts with human polynucleotide kinase in addition to its established interactions with DNA polymerase-beta and DNA ligase III. Moreover, these four proteins are coassociated in multiprotein complexes in human cell extract and together they repair single-strand breaks typical of those induced by reactive oxygen species and ionizing radiation. Strikingly, XRCC1 stimulates the DNA kinase and DNA phosphatase activities of polynucleotide kinase at damaged DNA termini and thereby accelerates the overall repair reaction. These data identify a novel pathway for mammalian single-strand break repair and demonstrate a concerted role for XRCC1 and PNK in the initial step of processing damaged DNA ends.
引用
收藏
页码：107 / 117
页数：11
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