Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
J Cell Sci. 2020 Dec 4;133(23):jcs248831. doi: 10.1242/jcs.248831.
Precise control of chromosome dynamics during meiosis is critical for fertility. A gametocyte undergoing meiosis coordinates formation of the synaptonemal complex (SC) to promote efficient homologous chromosome recombination. Subsequent disassembly of the SC occurs prior to segregation of homologous chromosomes during meiosis I. We examined the requirements of the mammalian Aurora kinases (AURKA, AURKB and AURKC) during SC disassembly and chromosome segregation using a combination of chemical inhibition and gene deletion approaches. We find that both mouse and human spermatocytes fail to disassemble SC lateral elements when the kinase activity of AURKB and AURKC are chemically inhibited. Interestingly, both conditional knockout and knockout mouse spermatocytes successfully progress through meiosis, and the mice are fertile. In contrast, , double knockout spermatocytes fail to coordinate disassembly of SC lateral elements with chromosome condensation and segregation, resulting in delayed meiotic progression. In addition, deletion of and leads to an accumulation of metaphase spermatocytes, chromosome missegregation and aberrant cytokinesis. Collectively, our data demonstrate that AURKB and AURKC functionally compensate for one another ensuring successful mammalian spermatogenesis.This article has an associated First Person interview with the first author of the paper.
在减数分裂过程中精确控制染色体动力学对于生育能力至关重要。处于减数分裂过程中的配子细胞协调联会复合体（SC）的形成，以促进同源染色体重组的有效发生。随后，在减数分裂 I 过程中同源染色体分离之前，SC 会发生解体。我们使用化学抑制和基因缺失方法的组合，研究了哺乳动物 Aurora 激酶（AURKA、AURKB 和 AURKC）在 SC 解体和染色体分离过程中的需求。我们发现，当 AURKB 和 AURKC 的激酶活性被化学抑制时，小鼠和人精子细胞都无法解联会 SC 侧元件。有趣的是，条件性敲除和敲除小鼠的精子细胞都能成功地通过减数分裂，并且这些小鼠具有生育能力。相比之下，双敲除的精子细胞无法协调联会 SC 侧元件的解体与染色体浓缩和分离，导致减数分裂进程延迟。此外， 缺失会导致中期精子细胞积累、染色体错误分离和异常胞质分裂。总的来说，我们的数据表明 AURKB 和 AURKC 能够相互代偿，确保了哺乳动物精子发生的成功。本文有一篇与论文第一作者的第一人称访谈。
