Miyazaki Seira, Kim Jihye, Yamagishi Yuya, Ishiguro Tadashi, Okada Yuki, Tanno Yuji, Sakuno Takeshi, Watanabe Yoshinori
Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Tokyo, 113-0033, Japan.
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Tokyo, 113-0032, Japan.
Genes Cells. 2017 Jun;22(6):552-567. doi: 10.1111/gtc.12496. Epub 2017 May 12.
In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1. Consequently, in contrast to the transient kinetochore localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic analyses show a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin that is important for establishing meiosis-specific chromosome segregation. We provide evidence that the meiosis-specific Bub1 regulation is conserved in mouse.
在减数分裂I中，姐妹染色单体被来自同一极的微管捕获（单极定向），并且着丝粒凝聚力在整个后期都受到保护。依赖于Bub1激酶对组蛋白H2A的磷酸化而定位于着丝粒的守护蛋白，在保护减数分裂黏连蛋白Rec8免受分离酶切割方面发挥核心作用。另一个关键的减数分裂动粒因子，减数分裂激酶，可能调节黏连保护，尽管其潜在的分子机制仍然不清楚。在这里，我们表明，裂殖酵母Moa1（减数分裂激酶）在减数分裂I期间与着丝粒蛋白C稳定结合，将Plo1（类polo激酶）募集到动粒并磷酸化Spc7（KNL1）以积累Bub1。因此，与有丝分裂Bub1在动粒的短暂定位不同，减数分裂Bub1在动粒持续存在直到后期I。减数分裂Bub1库通过与结合并稳定守护蛋白1的异染色质蛋白Swi6合作，确保守护蛋白1在着丝粒的强大定位和黏连保护。此外，分子遗传学分析表明，减数分裂激酶和守护蛋白对着丝粒黏连保护有层次调节，这对于建立减数分裂特异性染色体分离很重要。我们提供证据表明，减数分裂特异性Bub1调节在小鼠中是保守的。
