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小鼠卵母细胞中延长的中期II停滞会削弱极光激酶B/C依赖性的错误校正。

Prolonged metaphase II arrest weakens Aurora B/C-dependent error correction in mouse oocytes.

作者信息

Langeoire Antoine, Kem-Seng Alison, Cladière Damien, Wassmann Katja, Buffin Eulalie

机构信息

Université Paris Cité, CNRS, Institut Jacques Monod, 15 rue Hélène Brion, 75013 Paris, France; Sorbonne Université, Institut de Biologie Paris Seine, 9 quai St. Bernard, 75252 Paris, France; CNRS UMR7622, Developmental Biology Lab, Sorbonne Université, 9 quai St. Bernard, 75252 Paris, France.

Sorbonne Université, Institut de Biologie Paris Seine, 9 quai St. Bernard, 75252 Paris, France; CNRS UMR7622, Developmental Biology Lab, Sorbonne Université, 9 quai St. Bernard, 75252 Paris, France.

出版信息

Curr Biol. 2025 May 5;35(9):2019-2031.e4. doi: 10.1016/j.cub.2025.03.030. Epub 2025 Apr 10.

Abstract

Chromosome segregation during meiosis is highly error-prone in mammalian oocytes. The mechanisms controlling chromosome attachments and the spindle assembly checkpoint (SAC) have been extensively studied in meiosis I, but our knowledge of these mechanisms during meiosis II is rather limited. Although mammalian oocytes arrest in metaphase II for an extended period awaiting fertilization, some misattached chromosomes may persist. This suggests that the mechanism correcting misattachments is not fully functional during the arrest. In this study, we investigated whether low inter-kinetochore tension, which characterizes incorrect attachments, can be detected by Aurora B/C-dependent error correction in meiosis II. We found that low tension, induced by low dose of STLC in early metaphase II, does indeed mediate microtubule detachment by Aurora B/C and, consequently, anaphase II delay through SAC activation. Surprisingly, we also found that, during prolonged metaphase II arrest, Aurora B/C activity is no longer sufficient to detach low-tension attachments, correlating with high accumulation of PP2A at kinetochores. As a result, the SAC is not activated, and sister chromatids segregate in anaphase II without delay even in the presence of low tension. Hence, during the prolonged metaphase II arrest to await fertilization, oocytes become unable to discriminate between correct and incorrect attachments and may allow errors to persist.

摘要

在哺乳动物卵母细胞中,减数分裂期间的染色体分离极易出错。在减数分裂I中,控制染色体附着和纺锤体组装检查点(SAC)的机制已得到广泛研究,但我们对减数分裂II期间这些机制的了解相当有限。尽管哺乳动物卵母细胞在中期II停滞较长时间等待受精,但一些错误附着的染色体可能会持续存在。这表明在停滞期间,纠正错误附着的机制并未完全发挥作用。在本研究中,我们调查了在减数分裂II中,以错误附着为特征的低动粒间张力是否能被Aurora B/C依赖性错误校正检测到。我们发现,在中期II早期由低剂量STLC诱导的低张力确实通过Aurora B/C介导微管脱离,从而通过SAC激活导致后期II延迟。令人惊讶的是,我们还发现,在中期II长期停滞期间,Aurora B/C活性不再足以脱离低张力附着,这与动粒处PP2A的高积累相关。结果,SAC未被激活,即使存在低张力,姐妹染色单体也在后期II无延迟地分离。因此,在中期II长期停滞等待受精期间,卵母细胞变得无法区分正确和错误的附着,可能会使错误持续存在。

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