Srs2 helicase prevents the formation of aberrant DNA damage during late prophase I of yeast meiosis
Srs2 helicase prevents the formation of aberrant DNA damage during late prophase I of yeast meiosis
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Srs2 解旋酶可防止酵母减数分裂前期 I 期间异常 DNA 损伤的形成
DOI：
10.1007/s00412-019-00709-5
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发表时间：
2019
期刊：
影响因子：
1.6
通讯作者：
and A. Shinohara
中科院分区：
文献类型：
--
作者：
Sasanuma;H.;Sabhan;H.M.S.;Furihata;Y.;Challa;K.;Palmer;L. Gasser;S.M.;Shinohara;M.;and A. Shinohara
正确修复双链断裂（DSB）是确保染色体正确分离的关键。在这项研究中，我们发现，删除theSRS 2基因，它编码的DNA解旋酶控制同源重组，诱导异常的染色体分离过程中芽殖酵母减数分裂。这种异常的染色体分离在rs 2细胞中伴随着一种新的DNA损伤的形成，这种DNA损伤在晚减数分裂前期I诱导。损伤可能包含长链单链DNA（ssDNA），导致ssDNA结合蛋白RPA和RecA同源物Rad 51以及细胞核内其他重组蛋白的聚集形成，但不是减数分裂特异性Dmc 1。在rs 2突变体中，Rad 51聚集体的形成依赖于减数分裂重组的启动，并且在没有染色体分离的情况下发生。重要的是，作为早期重组中间体，我们在rs 2突变体中检测到两个Rad 51焦点之间的Rad 51的薄桥，这在野生型中很少见。这可能是DSB两端连接和/或多浸润的细胞学表现。在thesrs 2突变体中，Rad 51聚集体的DNA损伤通过后期I和II，表明在粗线期阶段后没有DNA损伤诱导的细胞周期停滞。我们认为Srs 2解旋酶分解早期蛋白质-DNA重组中间体，以抑制晚期前期I期间异常致死性DNA损伤的形成。
Proper repair of double-strand breaks (DSBs) is key to ensure proper chromosome segregation. In this study, we found that the deletion of theSRS2gene, which encodes a DNA helicase necessary for the control of homologous recombination, induces aberrant chromosome segregation during budding yeast meiosis. This abnormal chromosome segregation insrs2cells accompanies the formation of a novel DNA damage induced during late meiotic prophase I. The damage may contain long stretches of single-stranded DNAs (ssDNAs), which lead to aggregate formation of a ssDNA binding protein, RPA, and a RecA homolog, Rad51, as well as other recombination proteins inside of the nuclei, but not that of a meiosis-specific Dmc1. The Rad51 aggregate formation in thesrs2mutant depends on the initiation of meiotic recombination and occurs in the absence of chromosome segregation. Importantly, as an early recombination intermediate, we detected a thin bridge of Rad51 between two Rad51 foci in thesrs2mutant, which is rarely seen in wild type. These might be cytological manifestation of the connection of two DSB ends and/or multi-invasion. The DNA damage with Rad51 aggregates in thesrs2mutant is passed through anaphases I and II, suggesting the absence of DNA damage-induced cell cycle arrest after the pachytene stage. We propose that Srs2 helicase resolves early protein-DNA recombination intermediates to suppress the formation of aberrant lethal DNA damage during late prophase I.