Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis

Abstract

The establishment of metaphase chromosomes is an essential prerequisite of sister chromatid separation in anaphase. It involves the coordinated action of cohesin and condensin, protein complexes that mediate cohesion and condensation, respectively. In metazoans, most cohesin dissociates from chromatin at prophase, coincident with association of condensin. Whether loosening of cohesion at the onset of mitosis facilitates the compaction process, resolution of the sister chromatids, or both, remains unknown. We have found that the prophase release of cohesin is completely blocked when two mitotic kinases, aurora B and polo-like kinase (Plx1), are simultaneously depleted from Xenopus egg extracts. Condensin loading onto chromatin is not affected under this condition, and rod-shaped chromosomes are produced that show an apparently normal level of compaction. However, the resolution of sister chromatids within these chromosomes is severely compromised. This is not because of inhibition of topoisomerase II activity that is also required for the resolution process. We propose that aurora B and Plx1 cooperate to destabilize the sister chromatid linkage through distinct mechanisms that may involve phosphorylation of histone H3 and cohesin, respectively. More importantly, our results strongly suggest that cohesin release at the onset of mitosis is essential for sister chromatid resolution but not for condensin-mediated compaction.

A topoisomerase II-dependent mechanism for resetting replicons at the S–M-phase transition

“…However, H1 kinase activity was not changed in the absence of topo II (Lemaitre et al 2005) and the cdkdependent chromatin binding/dissociation of condensin/ cohesin was not drastically affected, supporting previous data using topo II inhibitors ( Fig. 1C; Losada et al 2002). Furthermore, we did not observe changes in chromatin assembly, as judged by measurements of nucleosome assembly and nucleosome spacing (Supplemental Fig.…”

Getting in and out of mitosis with Polo-like kinase-1

“…The initial examination of Polo mutants in Drosophila revealed hypercondensed chromosomes (Llamazares et al, 1991). These observations matched later studies that described condensation defects when Plk1-function was interfered with (Losada et al, 2002;Gimenez-Abian et al, 2004;van Vugt et al, 2004a). In contrast to condensin recruitment, for which no direct involvement for Pololike kinases is described, cohesin removal is directly regulated by Plk's.…”

Quantitative Phospho-proteomics to Investigate the Polo-like Kinase 1-Dependent Phospho-proteome

“…In prometaphase, PLK1 is required for the generation of stable kinetochoremicrotubule attachments (7)(8)(9)(10). PLK1 also promotes dissociation of cohesin from chromosome arms in prophase and prometaphase by phosphorylating cohesin's STAG2 subunit (11)(12)(13)(14), as well as multiple aspects of cytokinesis by phosphorylating activators and effectors of RhoA (1,15).…”