在酵母减数分裂过程中,Rad51 活性的下调可防止其与 Dmc1 竞争修复双链断裂。

Down-regulation of Rad51 activity during meiosis in yeast prevents competition with Dmc1 for repair of double-strand breaks.

机构信息

Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, United States of America.

Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America.

出版信息

PLoS Genet. 2014 Jan;10(1):e1004005. doi: 10.1371/journal.pgen.1004005. Epub 2014 Jan 23.

Abstract

Interhomolog recombination plays a critical role in promoting proper meiotic chromosome segregation but a mechanistic understanding of this process is far from complete. In vegetative cells, Rad51 is a highly conserved recombinase that exhibits a preference for repairing double strand breaks (DSBs) using sister chromatids, in contrast to the conserved, meiosis-specific recombinase, Dmc1, which preferentially repairs programmed DSBs using homologs. Despite the different preferences for repair templates, both Rad51 and Dmc1 are required for interhomolog recombination during meiosis. This paradox has recently been explained by the finding that Rad51 protein, but not its strand exchange activity, promotes Dmc1 function in budding yeast. Rad51 activity is inhibited in dmc1Δ mutants, where the failure to repair meiotic DSBs triggers the meiotic recombination checkpoint, resulting in prophase arrest. The question remains whether inhibition of Rad51 activity is important during wild-type meiosis, or whether inactivation of Rad51 occurs only as a result of the absence of DMC1 or checkpoint activation. This work shows that strains in which mechanisms that down-regulate Rad51 activity are removed exhibit reduced numbers of interhomolog crossovers and noncrossovers. A hypomorphic mutant, dmc1-T159A, makes less stable presynaptic filaments but is still able to mediate strand exchange and interact with accessory factors. Combining dmc1-T159A with up-regulated Rad51 activity reduces interhomolog recombination and spore viability, while increasing intersister joint molecule formation. These results support the idea that down-regulation of Rad51 activity is important during meiosis to prevent Rad51 from competing with Dmc1 for repair of meiotic DSBs.

摘要

同源重组在促进减数分裂染色体正确分离中起着关键作用,但对这一过程的机制理解还远远不够。在营养细胞中,Rad51 是一种高度保守的重组酶,它表现出使用姐妹染色单体修复双链断裂 (DSB) 的偏好,而保守的减数分裂特异性重组酶 Dmc1 则优先使用同源物修复有丝分裂 DSB。尽管修复模板的偏好不同,但 Rad51 和 Dmc1 都需要在减数分裂中进行同源重组。最近的研究发现,Rad51 蛋白而非其链交换活性促进了芽殖酵母中 Dmc1 的功能,从而解释了这一悖论。在 dmc1Δ 突变体中,Rad51 活性受到抑制,因为不能修复减数分裂 DSB 会触发减数分裂重组检查点,导致前期停滞。问题仍然是 Rad51 活性的抑制在野生型减数分裂中是否重要,或者 Rad51 的失活是否仅因缺乏 DMC1 或检查点激活而发生。这项工作表明,去除下调 Rad51 活性的机制的菌株表现出同源重组交叉和非交叉的数量减少。一个功能减弱的突变体 dmc1-T159A 形成的预突触丝不太稳定,但仍然能够介导链交换并与辅助因子相互作用。将 dmc1-T159A 与上调的 Rad51 活性结合使用会减少同源重组和孢子活力,同时增加姐妹染色单体连接分子的形成。这些结果支持这样一种观点,即在减数分裂中下调 Rad51 活性对于防止 Rad51 与 Dmc1 竞争修复减数分裂 DSB 是很重要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/679c/3900393/6319d7c642fe/pgen.1004005.g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索