PP2A Is Required for Centromeric Localization of Sgo1 and Proper Chromosome Segregation

Zhanyun Tang, Hongjun Shu, Wei Qi, Nadir A. Mahmood, Marc C. Mumby, Hongtao Yu

Research output: Contribution to journalArticlepeer-review

276 Scopus citations

Abstract

Loss of sister-chromatid cohesion triggers chromosome segregation in mitosis and occurs through two mechanisms in vertebrate cells: (1) phosphorylation and removal of cohesin from chromosome arms by mitotic kinases, including Plk1, during prophase, and (2) cleavage of centromeric cohesin by separase at the metaphase-anaphase transition. Bub1 and the MEI-S332/Shugoshin (Sgo1) family of proteins protect centromeric cohesin from mitotic kinases during prophase. We show that human Sgo1 binds to protein phosphatase 2A (PP2A). PP2A localizes to centromeres in a Bub1-dependent manner. The Sgo1-PP2A interaction is required for centromeric localization of Sgo1 and proper chromosome segregation in human cells. Depletion of Plk1 by RNA interference (RNAi) restores centromeric localization of Sgo1 and prevents chromosome missegregation in cells depleted of PP2A_Aα. Our findings suggest that Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting Plk1-mediated chromosome removal of Sgo1.

Original languageEnglish (US)
Pages (from-to)575-585
Number of pages11
JournalDevelopmental cell
Volume10
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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