Mouse ANKRD31 Regulates Spatiotemporal Patterning of Meiotic Recombination Initiation and Ensures Recombination between X and Y Sex Chromosomes
Mouse ANKRD31 Regulates Spatiotemporal Patterning of Meiotic Recombination Initiation and Ensures Recombination between X and Y Sex Chromosomes
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DOI：
10.1016/j.molcel.2019.03.022
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发表时间：
2019-06-06
期刊：
影响因子：
16
通讯作者：
Toth, Attila
中科院分区：
文献类型：
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作者：
Papanikos, Frantzeskos;Clement, Julie A. J.;Toth, Attila
减数分裂过程中染色体的有序分离需要同源染色体之间通过重组形成交换。程序性DNA双链断裂（DSB）启动减数分裂重组。我们确定ANKRD31作为组装在减数分裂染色体轴上的DSB促进蛋白复合物的关键组分。全基因组，ANKRD31缺陷导致延迟重组启动。此外，ANKRD31的缺失改变了DSB的分布，因为对通常吸引DSB的位点的选择性降低。引人注目的是，ANKRD 31缺陷还消除了通常表征X和Y染色体的假常染色体区域（PAR）的独特的高重组率。因此，性染色体不形成交换，导致ANKRD31缺陷精母细胞中染色体分离失败。这些缺陷与在常染色体轴上组装DSB促进蛋白的全基因组延迟以及野生型中高度富集DSB促进蛋白的专门PAR轴结构域的丢失共同发生。因此，我们提出了一个模型的时空格局重组ANKRD31依赖控制轴相关的DSB促进蛋白。
Orderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a key component of complexes of DSB-promoting proteins that assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution because of reduced selectivity for sites that normally attract DSBs. Strikingly, ANKRD31 deficiency also abolishes uniquely high rates of recombination that normally characterize pseudoautosomal regions (PARs) of X and Y chromosomes. Consequently, sex chromosomes do not form cross-overs, leading to chromosome segregation failure in ANKRD31-deficient spermatocytes. These defects co-occur with a genome-wide delay in assembling DSB-promoting proteins on autosome axes and loss of a specialized PAR-axis domain that is highly enriched for DSB-promoting proteins in wild type. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated DSB-promoting proteins.