DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1
DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1
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DOI：
10.1038/nature02964
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发表时间：
2004-10-21
期刊：
影响因子：
64.8
通讯作者：
Foiani, M
中科院分区：
文献类型：
--
作者：
Ira, G;Pellicioli, A;Foiani, M
由HO内切核酸酶诱导的单个双链断裂（DSB）触发通过同源重组的修复和芽殖酵母中Mec 1依赖性DNA损伤检查点的激活（1-6）。在这里，我们报告说，DNA损伤检查点激活DSB需要细胞周期蛋白依赖性激酶CDK 1（Cdc 28）在芽殖酵母。CDK 1也需要在任何细胞周期阶段的DSB诱导的同源重组。通过使用类似物敏感的CDK 1蛋白抑制同源重组（7，8）导致非同源末端连接的补偿性增加。CDK 1是DSB末端的有效5'至3'切除以及单链DNA结合复合物RPA和Rad 51重组蛋白的募集所必需的。相反，Mre 11蛋白，MRX复合物的一部分，积累在未切除的DSB端。当DNA损伤检查点由核苷酸切除修复处理的病变启动时，不需要CDK 1。DSB诱导的检查点的维持需要持续的CDK 1活性，以确保持续的末端切除。CDK 1对于同源重组的后续步骤也很重要，在链侵入之后和新DNA合成开始之前。
A single double-strand break (DSB) induced by HO endonuclease triggers both repair by homologous recombination and activation of the Mec1-dependent DNA damage checkpoint in budding yeast(1-6). Here we report that DNA damage checkpoint activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding yeast. CDK1 is also required for DSB-induced homologous recombination at any cell cycle stage. Inhibition of homologous recombination by using an analogue-sensitive CDK1 protein(7,8) results in a compensatory increase in non-homologous end joining. CDK1 is required for efficient 5' to 3' resection of DSB ends and for the recruitment of both the single-stranded DNA-binding complex, RPA, and the Rad51 recombination protein. In contrast, Mre11 protein, part of the MRX complex, accumulates at unresected DSB ends. CDK1 is not required when the DNA damage checkpoint is initiated by lesions that are processed by nucleotide excision repair. Maintenance of the DSB-induced checkpoint requires continuing CDK1 activity that ensures continuing end resection. CDK1 is also important for a later step in homologous recombination, after strand invasion and before the initiation of new DNA synthesis.