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Vol. 16, No. 23, pp. 3004-3016, December 1, 2002
Cold Spring Harbor Laboratory, Cold Spring Harbor,
New York 11724, USA
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.
[Key Words: Cohesin; condensin; sister chromatid cohesion; chromosome condensation; histone H3 phosphorylation]
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