Mnd1 Is Required for Meiotic Interhomolog Repair
Mnd1 Is Required for Meiotic Interhomolog Repair
复制标题
DOI：
10.1016/j.cub.2004.04.030
复制
发表时间：
2004-05
期刊：
影响因子：
9.2
通讯作者：
C. Zierhut;M. Berlinger;C. Rupp;A. Shinohara;F. Klein
中科院分区：
文献类型：
--
作者：
C. Zierhut;M. Berlinger;C. Rupp;A. Shinohara;F. Klein
背景：虽然在减数分裂和有丝分裂过程中，双链断裂（DSB）修复对细胞的存活至关重要，但两种类型的细胞周期中修复的首选机制存在显著差异。因此，在减数分裂过程中，是同源染色体而不是姐妹染色单体被用作修复模板。结果：由于Mec1 dna损伤检查点的激活，在I前期没有Mnd1阻滞的情况下，细胞试图进行减数分裂，积累了过度切除的dsb和异常突触。孢子形成ofmnd1Δstrains可以通过删除red1orhop1来恢复，这允许使用姐妹染色单体作为修复模板来修复dsb。Mnd1作为病灶定位于染色质，独立于DSB形成、轴向元件（AE）形成和突触复合体（SC）形成，不与Rad51共定位。Mnd1并不优先与重组热点相关联。结论：我们的研究结果表明，Mnd1通过使用同源染色体作为修复模板特异性地促进DSB修复。Rec8、Red1或Hop1的存在使得Mnd1在DNA修复中不可或缺，可能是通过建立同源间（IH）偏倚。定位研究表明，Mnd1在没有被特异性招募到DNA修复位点的情况下实现了这一功能。我们提出了一个模型，其中Mnd1促进染色质可及性，这是允许链侵入减数分裂染色质所必需的。
Background:While double-strand break (DSB) repair is vital to the survival of cells during both meiosis and mitosis, the preferred mechanism of repair differs drastically between the two types of cell cycle. Thus, during meiosis, it is the homologous chromosome rather than the sister chromatid that is used as a repair template.Results:Cells attempting to undergo meiosis in the absence of Mnd1 arrest in prophase I due to the activation of the Mec1 DNA-damage checkpoint accumulating hyperresected DSBs and aberrant synapsis. Sporulation ofmnd1Δstrains can be restored by deletingRED1orHOP1,which permits repair of DSBs by using the sister chromatid as a repair template. Mnd1 localizes to chromatin as foci independently of DSB formation, axial element (AE) formation, and synaptonemal complex (SC) formation and does not colocalize with Rad51. Mnd1 does not preferentially associate with hotspots of recombination.Conclusions:Our results suggest that Mnd1 acts specifically to promote DSB repair by using the homologous chromosome as a repair template. The presence of Rec8, Red1, or Hop1 renders Mnd1 indispensable for DNA repair, presumably through the establishment of interhomolog (IH) bias. Localization studies suggest that Mnd1 carries out this function without being specifically recruited to the sites of DNA repair. We propose a model in which Mnd1 facilitates chromatin accessibility, which is required to allow strand invasion in meiotic chromatin.