The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks
The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks
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DOI：
10.1038/nsmb1313
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发表时间：
2007-11-01
影响因子：
16.8
通讯作者：
Kanaar, Roland
中科院分区：
文献类型：
--
作者：
Hanada, Katsuhiro;Budzowska, Magda;Kanaar, Roland
基因组的忠实复制需要结构特定的内切酶，如大肠杆菌中的RuvABC复合体。这些酶有助于解决复制叉处的问题，这些问题已经被模板中的DNA破坏所扰乱。关于这些酶在哺乳动物细胞中的身份，我们知道的要少得多。MUS81是一种真核结构特异性内切酶的催化成分，它优先切割分支的DNA底物，使人想起复制和重组中间产物。在这里，我们探索MUS81维持染色体稳定性的机制。我们发现，MUS81参与了双链DNA断裂的形成，以响应复制的抑制。此外，在没有MUS81进行染色体处理的情况下，停滞的DNA复制叉的恢复会减弱，并出现染色体异常。我们认为，MUS81通过将潜在有害的复制相关DNA结构转化为更易于DNA修复的中间体来抑制染色体的不稳定性。
Faithful duplication of the genome requires structure-specific endonucleases such as the RuvABC complex in Escherichia coli. These enzymes help to resolve problems at replication forks that have been disrupted by DNA damage in the template. Much less is known about the identities of these enzymes in mammalian cells. Mus81 is the catalytic component of a eukaryotic structure-specific endonuclease that preferentially cleaves branched DNA substrates reminiscent of replication and recombination intermediates. Here we explore the mechanisms by which Mus81 maintains chromosomal stability. We found that Mus81 is involved in the formation of double-strand DNA breaks in response to the inhibition of replication. Moreover, in the absence of chromosome processing by Mus81, recovery of stalled DNA replication forks is attenuated and chromosomal aberrations arise. We suggest that Mus81 suppresses chromosomal instability by converting potentially detrimental replication-associated DNA structures into intermediates that are more amenable to DNA repair.