Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors.
Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors.
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DOI：
10.1016/j.cub.2011.03.003
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发表时间：
2011-04-26
期刊：
影响因子：
9.2
通讯作者：
Hunt, Patricia Ann
中科院分区：
文献类型：
--
作者：
Nagaoka, So Iha;Hodges, Craig A.;Albertini, David F.;Hunt, Patricia Ann
分离的同源染色体在第一次减数分裂（MI）是促进交叉和姐妹动粒，使他们能够使单极附件MI纺锤体的物理约束。同源物的分离失败或过早分离导致MI处的单价染色体，并且限制形成单极附件的单价体应该是固有地不稳定的并触发纺锤体组装检查点（SAC）。虽然这似乎是在男性的情况下，一个或几个单价体的存在不会导致哺乳动物卵母细胞的细胞周期延迟或停滞。SAC的纺锤体组装部分似乎在卵母细胞中正常发挥功能，但已经提出了两种假设来解释对单价染色体的惊人缺乏反应：1）卵母细胞SAC对异常染色体行为的严格性降低，以及2）单价体形成满足SAC要求的双极附着的能力。本研究的Mlh 1突变小鼠的结果表明，中期对齐是不是一个先决条件，为后期发作，并提供了强有力的证据，MI纺锤体稳定和后期发作需要稳定的双极连接的临界质量-但重要的是，不是所有-染色体。我们推测，在SAC介导的控制的细微差异，使人类卵母细胞固有的错误倾向，并提供了一个生物学解释人类的非整倍体的高比率。
Segregation of homologous chromosomes at the first meiotic division (MI) is facilitated by crossovers and by a physical constraint imposed on sister kinetochores that allows them to make a monopolar attachment to the MI spindle. Recombination failure or premature separation of homologs results in univalent chromosomes at MI, and univalents constrained to form monopolar attachments should be inherently unstable and trigger the spindle assembly checkpoint (SAC). Although this appears to be the case in the male, the presence of one or several univalents does not cause cell cycle delay or arrest in the mammalian oocyte. The spindle assembly portion of the SAC appears to function normally in the oocyte, but two hypotheses have been proposed to explain the surprising lack of response to univalent chromosomes: 1) reduced stringency of the oocyte SAC to aberrant chromosome behavior, and 2) the ability of univalents to form bipolar attachments that satisfy SAC requirements. Results of the present study of Mlh1 mutant mice demonstrate that metaphase alignment is not a prerequisite for anaphase onset and provide strong evidence that MI spindle stabilization and anaphase onset requires stable bipolar attachment of a critical mass - but, importantly, not all - chromosomes. We postulate that subtle differences in SAC-mediated control make the human oocyte inherently error-prone and provide a biological explanation for the high rate of aneuploidy in humans.
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