Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice.

Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice.
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DOI:
10.1083/jcb.145.7.1395
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发表时间:
1999-06-28
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Hunt PA
Hunt PA
中科院分区:
其他
文献类型:
--
作者:
Woods LM;Hodges CA;Baart E;Baker SM;Liskay M;Hunt PA

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在小鼠卵母细胞中,第一个减数分裂纺锤体是通过多个微管组织中心而不是一对中心体的作用形成的。虽然染色体被认为在组织减数分裂纺锤体中起主要作用,但仍不清楚稳定的双极纺锤体是如何建立的。我们研究了小鼠卵母细胞中第一个减数分裂纺锤体的形成,这些卵母细胞来自DNA错配修复基因Mlh1的靶向破坏纯合子小鼠。在没有MLH 1蛋白的情况下,减数分裂重组急剧减少,因此,绝大多数染色体在第一次减数分裂时以不配对的单价体存在。这些单价染色体在前中期的方向表明,他们无法建立稳定的双极纺锤体附件,大概是由于无法区分个别姐妹染色单体上的功能动粒结构域。在这种异常染色体行为的存在下,稳定的第一次减数分裂纺锤体不会形成,纺锤体两极继续伸长,绝大多数细胞永远不会启动后期。这些结果表明,在女性减数分裂系统中,纺锤体的形成是基于多个微管组织中心的作用,染色体不仅促进微管聚合和组织,但它们的附件相反的纺锤体极点的行为,以稳定形成纺锤体极点。
In mouse oocytes, the first meiotic spindle is formed through the action of multiple microtubule organizing centers rather than a pair of centrosomes. Although the chromosomes are thought to play a major role in organizing the meiotic spindle, it remains unclear how a stable bipolar spindle is established. We have studied the formation of the first meiotic spindle in murine oocytes from mice homozygous for a targeted disruption of the DNA mismatch repair gene, Mlh1. In the absence of the MLH1 protein meiotic recombination is dramatically reduced and, as a result, the vast majority of chromosomes are present as unpaired univalents at the first meiotic division. The orientation of these univalent chromosomes at prometaphase suggests that they are unable to establish stable bipolar spindle attachments, presumably due to the inability to differentiate functional kinetochore domains on individual sister chromatids. In the presence of this aberrant chromosome behavior a stable first meiotic spindle is not formed, the spindle poles continue to elongate, and the vast majority of cells never initiate anaphase. These results suggest that, in female meiotic systems in which spindle formation is based on the action of multiple microtubule organizing centers, the chromosomes not only promote microtubule polymerization and organization but their attachment to opposite spindle poles acts to stabilize the forming spindle poles.
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