Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest.

Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest.
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DOI:
10.1038/ncomms7946
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发表时间:
2015-04-21
影响因子:
16.6
通讯作者:
Wassmann, Katja
Wassmann, Katja
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Touati, Sandra A.;Buffin, Eulalie;Cladiere, Damien;Hached, Khaled;Rachez, Christophe;van Deursen, Jan M.;Wassmann, Katja

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哺乳动物雌性减数分裂是容易出错的,随着生殖寿命的结束,减数分裂染色体错误分离的比率强烈增加。在接近更年期的女性的卵母细胞和老年小鼠的卵巢中观察到BubR 1的强烈减少,这导致了BubR 1的逐渐下降导致与年龄相关的非整倍化的假设。在这里,我们采用了条件性敲除小鼠卵母细胞的方法来剖析BubR1减数分裂的作用。我们发现,BubR1是所需的不同的减数分裂功能,包括持续的纺锤体组装检查点活动,减数分裂I的时间和建立强大的着丝粒微管附件在减数分裂特异性的方式,但不是前期I逮捕。这些数据表明,BubR 1在第一次减数分裂期间的染色体分离中发挥着多方面的作用,并表明BubR 1与年龄相关的下降是女性接近更年期时非整倍体卵母细胞形成的关键决定因素。
Mammalian female meiosis is error prone, with rates of meiotic chromosome missegregations strongly increasing towards the end of the reproductive lifespan. A strong reduction of BubR1 has been observed in oocytes of women approaching menopause and in ovaries of aged mice, which led to the hypothesis that a gradual decline of BubR1 contributes to age-related aneuploidization. Here we employ a conditional knockout approach in mouse oocytes to dissect the meiotic roles of BubR1. We show that BubR1 is required for diverse meiotic functions, including persistent spindle assembly checkpoint activity, timing of meiosis I and the establishment of robust kinetochore-microtubule attachments in a meiosis-specific manner, but not prophase I arrest. These data reveal that BubR1 plays a multifaceted role in chromosome segregation during the first meiotic division and suggest that age-related decline of BubR1 is a key determinant of the formation of aneuploid oocytes as women approach menopause.
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