Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.
J Cell Biol. 2013 Jul 22;202(2):221-9. doi: 10.1083/jcb.201303019. Epub 2013 Jul 15.
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.
有丝分裂过程中染色体的分离依赖于动粒与纺锤体微管的稳定结合。有丝分裂纺锤体的形成和动粒-微管(K-MT)捕获通常在核膜破裂后几分钟内发生。相比之下,在小鼠卵母细胞的减数分裂 I 中,无中心体的双极纺锤体的形成需要 3-4 小时,并且 K-MT 附着的稳定化还会延迟 3-4 小时。导致这种延迟的机制(可能防止了纺锤体形成过程中错误附着的稳定化)尚不清楚。在这里,我们发现在减数分裂 I 期间,附着受到 CDK1 活性的调节,CDK1 活性在前期和中期逐渐增加。CDK1 活性的部分降低会延迟稳定附着的形成,而 CDK1 活性的过早增加则会导致稳定附着的过早形成,并最终导致有丝分裂 I 后期的染色体滞后。这些结果表明,减数分裂 I 中 CDK1 活性的缓慢增加充当了一个定时机制,只有在双极纺锤体形成后才允许稳定的 K-MT 附着,从而防止附着错误。