Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I.
Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I.
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DOI：
10.1083/jcb.201303019
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发表时间：
2013-07-22
期刊：
影响因子：
--
通讯作者：
Lampson MA
中科院分区：
文献类型：
--
作者：
Davydenko O;Schultz RM;Lampson MA
减数分裂 I 中 CDK1 活性的缓慢增加充当计时机制，仅在双极纺锤体形成后才允许稳定的动粒-微管附着，从而防止附着错误。细胞分裂过程中的染色体分离取决于动粒与纺锤体微管的稳定附着。有丝分裂纺锤体的形成和动粒微管（K-MT）捕获通常发生在核膜破裂后的几分钟内。相比之下，在小鼠卵母细胞减数分裂 I 期间，心粒体双极纺锤体的形成需要 3-4 小时，并且 K-MT 附着的稳定又延迟了 3-4 小时。造成这种延迟的机制尚不清楚，这种延迟可能会阻止纺锤体形成过程中错误附件的稳定。在这里，我们表明，在减数分裂 I 期间，附着物受到 CDK1 活性的调节，CDK1 活性在中期和中期 I 中逐渐增加。CDK1 活性的部分降低延迟了稳定附着物的形成，而 CDK1 活性的过早增加导致稳定附着物的过早形成，并最终在后期 I 滞后染色体。这些结果表明，减数分裂 I 中 CDK1 活性的缓慢增加充当了一种定时机制，仅在双极纺锤体形成后才允许稳定的 K-MT 附着。从而防止附件错误。
The slow increase in CDK1 activity in meiosis I acts as a timing mechanism to allow stable kinetochore–microtubule attachments only after bipolar spindle formation, thus preventing attachment errors. Chromosome segregation during cell division depends on stable attachment of kinetochores to spindle microtubules. Mitotic spindle formation and kinetochore–microtubule (K-MT) capture typically occur within minutes of nuclear envelope breakdown. In contrast, during meiosis I in mouse oocytes, formation of the acentrosomal bipolar spindle takes 3–4 h, and stabilization of K-MT attachments is delayed an additional 3–4 h. The mechanism responsible for this delay, which likely prevents stabilization of erroneous attachments during spindle formation, is unknown. Here we show that during meiosis I, attachments are regulated by CDK1 activity, which gradually increases through prometaphase and metaphase I. Partial reduction of CDK1 activity delayed formation of stable attachments, whereas a premature increase in CDK1 activity led to precocious formation of stable attachments and eventually lagging chromosomes at anaphase I. These results indicate that the slow increase in CDK1 activity in meiosis I acts as a timing mechanism to allow stable K-MT attachments only after bipolar spindle formation, thus preventing attachment errors.
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