Department of Cell Biology, University of Virginia, School of Medicine, Charlottesville, VA, USA.
Department of Biochemistry and Molecular Genetics, University of Virginia, School of Medicine, Charlottesville, VA, USA.
Nat Cell Biol. 2019 Sep;21(9):1127-1137. doi: 10.1038/s41556-019-0376-4. Epub 2019 Sep 3.
The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere.
着丝粒内部是有丝分裂染色体上的一个区域，使能特定的生化反应，这些反应是某些特性的基础，如保持着丝粒的黏合性、动粒的调节以及特殊染色质的组装，这些特性能够抵抗微管的拉力。染色体乘客复合物（CPC）大量定位于着丝粒内部，目前尚不清楚它是否参与非激酶活性，这些非激酶活性有助于产生这些独特的染色质特性。我们发现，CPC 的 borealin 亚基在低于着丝粒内部浓度的浓度下，可在体外驱动 CPC 的相分离。我们还提供了强有力的证据表明，CPC 在着丝粒内部处于相分离状态。CPC 的相分离对于其在有丝分裂期间在内着丝粒的定位和功能是必需的。我们认为，CPC 结合相分离、激酶和组蛋白编码读取活性，以在着丝粒内部形成具有独特生化活性的染色质体。
