Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA
Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and termini of DNA
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DOI：
10.1038/sj.onc.1202922
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发表时间：
1999-09-16
期刊：
影响因子：
8
通讯作者：
Tsuruo, T
中科院分区：
文献类型：
--
作者：
Yamane, K;Tsuruo, T
BRCT区域是BRCA 1（乳腺癌易感基因1产物）的羧基末端，是与DNA修复酶和细胞周期调节因子中的区域同源的普遍存在的区域。我们发现，BRCT区域结合的DNA片段，使用TopBP 1蛋白（拓扑异构酶II结合蛋白1），与8个BRCT作为模型蛋白。这种结合与DNA序列、DNA末端的形式和能量无关。BRCT-DNA复合物显示出对核酸外切酶的抗性，表明BRCT结合的BNA断裂。BRCTs还结合DNA切口，这表明BRCTs在检测单链和双链DNA断裂或末端中起重要作用。另一方面，BRCT不与环状完整DNA结合，BRCA 1的BRCT也与DNA末端结合。由于某些BRCT是某些肿瘤组织中独特的通用元件，这些发现将揭示肿瘤抑制机制的新方面。
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.