Rad52 promotes postinvasion steps of meiotic double-strand-break repair

Rad52 promotes postinvasion steps of meiotic double-strand-break repair
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DOI:
10.1016/j.molcel.2007.12.014
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发表时间:
2008-02-29
期刊:
影响因子:
16
通讯作者:
Hunter, Neil
Hunter, Neil
中科院分区:
生物学1区
文献类型:
--
作者:
Lao, Jessica P.;Oh, Steve D.;Hunter, Neil

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在DNA双链断裂(DSB)的重组修复过程中,断裂的染色体使用同源染色体作为修复模板。重组的早期步骤有很好的特征:DSB末端组装reca家族蛋白的细丝,催化同源配对和链入侵反应。相比之下,入侵后的重组步骤却没有得到很好的描述。Rad52通过介导RecA同源物Rad51组装到核蛋白细丝中,在重组的早期阶段起着至关重要的作用。然而,减数分裂特异性的reca同源物Dmc1没有表现出这种依赖性。通过利用Dmcl的Rad52独立性,我们发现Rac152促进了酿酒酵母减数分裂重组的交叉和非交叉途径的入侵后步骤。这种活性存在于Rad52的n端区域,该区域可以退火互补的DNA链,并且独立于rad51组装功能。我们的研究结果表明,Rac152在时间和生物化学上不同的反应中起作用,并表明在重组过程中DSB末端重新结合的一般退火机制。
During DNA double-strand-break (DSB) repair by recombination, the broken chromosome uses a homologous chromosome as a repair template. Early steps of recombination are well characterized: DSB ends assemble filaments of RecA-family proteins that catalyze homologous pairing and strand-invasion reactions. By contrast, the postinvasion steps of recombination are poorly characterized. Rad52 plays an essential role during early steps of recombination by mediating assembly of a RecA homolog, Rad51, into nucleoprotein filaments. The meiosis-specific RecA-homolog Dmc1 does not show this dependence, however. By exploiting the Rad52 independence of Dmcl, we reveal that Rac152 promotes postinvasion steps of both crossover and noncrossover pathways of meiotic recombination in Saccharomyces cerevisiae. This activity resides in the N-terminal region of Rad52, which can anneal complementary DNA strands, and is independent of its Rad51-assembly function. Our findings show that Rac152 functions in temporally and biochemically distinct reactions and suggest a general annealing mechanism for reuniting DSB ends during recombination.