Separase Is Recruited to Mitotic Chromosomes to Dissolve Sister Chromatid Cohesion in a DNA-Dependent Manner

Yuxiao Sun, Martin Kucej, Heng Yu Fan, Hong Yu, Qing Yuan Sun, Hui Zou

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Sister chromatid separation is triggered by the separase-catalyzed cleavage of cohesin. This process is temporally controlled by cell-cycle-dependent factors, but its biochemical mechanism and spatial regulation remain poorly understood. We report that cohesin cleavage by human separase requires DNA in a sequence-nonspecific manner. Separase binds to DNA in vitro, but its proteolytic activity, measured by its autocleavage, is not stimulated by DNA. Instead, biochemical characterizations suggest that DNA mediates cohesin cleavage by bridging the interaction between separase and cohesin. In human cells, a fraction of separase localizes to the mitotic chromosome. The importance of the chromosomal DNA in cohesin cleavage is further demonstrated by the observation that the cleavage of the chromosome-associated cohesins is sensitive to nuclease treatment. Our observations explain why chromosome-associated cohesins are specifically cleaved by separase and the soluble cohesins are left intact in anaphase.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalCell
Volume137
Issue number1
DOIs
StatePublished - Apr 3 2009

Keywords

  • CELLBIO
  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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