Hierarchical Regulation of Centromeric Cohesion Protection by Meikin and Shugoshin during Meiosis I.
The kinetochore is the key apparatus regulating chromosome segregation. Particularly in meiosis, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation), and sister chromatid cohesion mediated by cohesin is protected at centromeres in the following anaphase. Shugoshin, which localizes 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, Moa1 (meikin), which was initially characterized as a mono-orientation factor in fission yeast, also regulates cohesion protection. Moa1, which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1), inducing the persistent accumulation of Bub1 at kinetochores. 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. Further, molecular genetic analyses reveal a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin during meiosis I.
Miyazaki S, Kim J, Sakuno T, Watanabe Y