Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair
Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair
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DOI：
10.1073/pnas.0908258106
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发表时间：
2009-12-15
影响因子：
11.1
通讯作者：
Zhao, Xiaolan
中科院分区：
文献类型：
--
作者：
Chen, Yu-Hung;Choi, Koyi;Zhao, Xiaolan
进化上保守的Smc 5/6复合体与重组修复有关，但其在此过程中的功能一直难以捉摸。在这里，我们报告，芽殖酵母Smc 5/6复合物直接结合到DNA解旋酶Mph 1。mph 1及其解旋酶活性定义了一个复制相关的重组子途径。我们发现，当Smc 5/6复合物有缺陷时，这种途径是有毒的，因为mph 1 Delta及其解旋酶突变抑制Smc 5/6复合物突变体中的多种缺陷，包括它们对复制阻断剂的敏感性，生长缺陷和低效的染色单体分离，而MPH 1过表达加剧了这些缺陷。我们进一步证明，Mph 1和它的解旋酶活性在很大程度上负责潜在的有害重组中间体的Smc 5/6复合物的突变体的积累。我们还提供了证据表明，mph 1 Delta并不能减轻缺乏Sgs 1的细胞对DNA损伤或重组中间产物积累的敏感性，Sgs 1被认为与Smc 5/6复合物一起发挥作用。因此，我们的研究结果揭示了Smc 5/6复合物在Mph 1依赖的重组子途径，这是不同的SGS 1的功能。我们认为Smc 5/6复合物可以抵消/调节Mph 1的促重组功能或促进Mph 1产生的重组结构的解析。
The evolutionarily conserved Smc5/6 complex is implicated in recombinational repair, but its function in this process has been elusive. Here we report that the budding yeast Smc5/6 complex directly binds to the DNA helicase Mph1. Mph1 and its helicase activity define a replication-associated recombination subpathway. We show that this pathway is toxic when the Smc5/6 complex is defective, because mph1 Delta and its helicase mutations suppress multiple defects in mutants of the Smc5/6 complex, including their sensitivity to replication-blocking agents, growth defects, and inefficient chromatid separation, whereas MPH1 overexpression exacerbates some of these defects. We further demonstrate that Mph1 and its helicase activity are largely responsible for the accumulation of potentially deleterious recombination intermediates in mutants of the Smc5/6 complex. We also present evidence that mph1 Delta does not alleviate sensitivity to DNA damage or the accumulation of recombination intermediates in cells lacking Sgs1, which is thought to function together with the Smc5/6 complex. Thus, our results reveal a function of the Smc5/6 complex in the Mph1-dependent recombinational subpathway that is distinct from Sgs1. We suggest that the Smc5/6 complex can counteract/modulate a pro-recombinogenic function of Mph1 or facilitate the resolution of recombination structures generated by Mph1.