Overlapping mechanisms promote postsynaptic RAD-51 filament disassembly during meiotic double-strand break repair.
Overlapping mechanisms promote postsynaptic RAD-51 filament disassembly during meiotic double-strand break repair.
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DOI：
10.1016/j.molcel.2009.12.026
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发表时间：
2010-01
期刊：
影响因子：
16
通讯作者：
Jordan D. Ward;D. Muzzini;Mark I. R. Petalcorin;E. Martinez-Perez;JULIE S. Martin;P. Plevani;G. Cassata;F. Marini;S. Boulton
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文献类型：
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作者：
Jordan D. Ward;D. Muzzini;Mark I. R. Petalcorin;E. Martinez-Perez;JULIE S. Martin;P. Plevani;G. Cassata;F. Marini;S. Boulton
同源重组（HR）是减数分裂DNA双链断裂（DSB）修复所必需的。尽管RAD-51-DNA丝组装和链交换的机制已被很好地表征，但HR的后续步骤还不太清楚。在这里，我们描述了一个合成的致命的相互作用之间的C。eleganshelicasehelq-1和RAD-51 paralogrfs-1，这导致在链侵入后阻断减数分裂DSB修复。尽管RAD-51-ssDNA丝在helq-1、rfs-1双突变体中以正常动力学在减数分裂DSB组装，RAD-51焦点的持续存在以及与rtel-1的遗传相互作用表明RAD-51未能从链侵入中间体中分解。事实上，纯化的HELQ-1和RFS-1在体外通过不同的机制独立地结合并促进RAD-51从双链而非单链DNA丝上的分解。这些结果表明，需要两个补偿活动，以促进突触后RAD-51丝拆卸，这是共同完成减数分裂DSB修复所必需的。
Homologous recombination (HR) is essential for repair of meiotic DNA double-strand breaks (DSBs). Although the mechanisms of RAD-51-DNA filament assembly and strand exchange are well characterized, the subsequent steps of HR are less well defined. Here, we describe a synthetic lethal interaction between theC. eleganshelicasehelq-1and RAD-51 paralogrfs-1, which results in a block to meiotic DSB repair after strand invasion. Whereas RAD-51-ssDNA filaments assemble at meiotic DSBs with normal kinetics inhelq-1, rfs-1double mutants, persistence of RAD-51 foci and genetic interactions withrtel-1suggest a failure to disassemble RAD-51 from strand invasion intermediates. Indeed, purified HELQ-1 and RFS-1 independently bind to and promote the disassembly of RAD-51 from double-stranded, but not single-stranded, DNA filaments via distinct mechanisms in vitro. These results indicate that two compensating activities are required to promote postsynaptic RAD-51 filament disassembly, which are collectively essential for completion of meiotic DSB repair.