Quartuccio Suzanne M, Dipali Shweta S, Schindler Karen
Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854.
Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854
Mol Biol Cell. 2017 Aug 15;28(17):2233-2240. doi: 10.1091/mbc.E16-12-0850. Epub 2017 Jun 28.
Aneuploidy is the leading genetic abnormality contributing to infertility, and chromosome segregation errors are common during female mammalian meiosis I (MI). Previous results indicate that haspin kinase regulates resumption of meiosis from prophase arrest, chromosome condensation, and kinetochore-microtubule attachments during early prometaphase of MI. Here we report that haspin inhibition in late prometaphase I causes acceleration of MI, bypass of the spindle assembly checkpoint (SAC), and loss of interchromatid axis-localized Aurora kinase C. Meiotic cells contain a second chromosomal passenger complex (CPC) population, with Aurora kinase B (AURKB) bound to INCENP. Haspin inhibition in oocytes from mice, where AURKB is the sole CPC kinase, does not alter MI completion timing, and no change in localization of the SAC protein, MAD2, is observed. These data suggest that AURKB on the interchromatid axis is not needed for SAC activation and illustrate a key difference between the functional capacities of the two AURK homologues.
非整倍体是导致不孕的主要遗传异常，染色体分离错误在雌性哺乳动物减数分裂I（MI）期间很常见。先前的结果表明，Haspin激酶在MI早期前中期调节减数分裂从前期阻滞的恢复、染色体凝聚以及动粒-微管附着。在此我们报告，在I期前中期后期抑制Haspin会导致MI加速、绕过纺锤体组装检查点（SAC）以及染色体间轴定位的极光激酶C丢失。减数分裂细胞包含第二个染色体乘客复合体（CPC）群体，其中极光激酶B（AURKB）与INCENP结合。在AURKB是唯一CPC激酶的小鼠卵母细胞中抑制Haspin，不会改变MI完成时间，并且未观察到SAC蛋白MAD2的定位变化。这些数据表明，染色体间轴上的AURKB对于SAC激活不是必需的，并说明了两种AURK同源物功能能力之间的关键差异。
