Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint

L. Sironi, M. Melixetian, M. Faretta, E. Prosperini, K. Helin, A. Musacchio

Research output: Contribution to journalArticle

Abstract

Mad2 is a key component of the spindle checkpoint, a device that controls the fidelity of chromosome segregation in mitosis. The ability of Mad2 to form oligomers in vitro has been correlated with its ability to block the cell cycle upon injection into Xenopus embryos. Here we show that Mad2 forms incompatible complexes with Mad1 and Cdc20, neither of which requires Mad2 oligomerization. A monomeric point mutant of Mad2 can sustain a cell cycle arrest of comparable strength to that of the wild-type protein. We show that the interaction of Mad2 with Mad1 is crucial for the localization of Mad2 to kinetochores, where Mad2 interacts with Cdc20. We propose a model that features the kinetochore as a 'folding factory' for the formation of a Mad2-Cdc20 complex endowed with inhibitory activity on the anaphase promoting complex.

Original languageEnglish
Pages (from-to)6371-6382
Number of pages12
JournalEMBO Journal
Volume20
Issue number22
DOIs
Publication statusPublished - Nov 15 2001

Keywords

  • Anaphase promoting complex
  • Cdc20
  • Mad1
  • Mad2
  • Mitotic spindle checkpoint

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

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