Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA

被引:75
作者
Yamane, K
Tsuruo, T
机构
[1] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan
[2] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Toshima Ku, Tokyo 1708455, Japan
关键词
checkpoint; Cut5; DNA damage sensor; DNA repair; Nijmegen breakage syndrome;
D O I
10.1038/sj.onc.1202922
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 BRCT region, the carboxyl-terminus of BRCA1 (the breast cancer susceptibility gene 1 product), is ubiquitous region homologous to regions in DNA repair enzymes and cell cycle regulators. We showed that the BRCT regions bound DNA fragments, using the TopBP1 protein (topoisomerase II binding protein 1), with eight BRCTs as a model protein. The bindings mere independent of DNA sequences, forms of DNA termini and energy. The BRCT-DNA complex showed resistance to an exonuclease, indicating that BRCT bound BNA breaks. The BRCTs also bound DNA nicks, suggesting that BRCTs play an important role in detection of both single- and double-strand DNA breaks or ends. On the other hand, BRCTs did not bind circular intact DNA, BRCTs of BRCA1 also bound DNA termini, Since some BRCTs are unique general elements in some tumor suppressions, these findings will reveal novel aspects of the tumor suppression mechanism.
引用
收藏
页码:5194 / 5203
页数:10
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