Running on a treadmill: Dynamic inhibition of APC/C by the spindle checkpoint

Laura A. Díaz-Martínez, Hongtao Yu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

During mitosis, the genome duplicated during S-phase is synchronously and accurately segregated to the two daughter cells. The spindle checkpoint prevents premature sister-chromatid separation and mitotic exit. The anaphase-promoting complex/cyclosome (APC/C) is a key target of the spindle checkpoint. Upon checkpoint activation, the mitotic checkpoint complex (MCC) containing Mad2, Bub3, Mad3/BubR1 and Cdc20 inhibits APC/C. Two independent studies in budding yeast have now shed light on the mechanism by which MCC inhibits APC/C. These studies indicate that Mad3 binds to the mitotic activator of APC/CCdc20 using peptide motifs commonly found in APC/C substrates and thus competes with APC/C substrates for APC/CCdc20 binding. In addition, Mad3 binding to APC/CCdc20 induces Cdc20 ubiquitination by APC/C, leading to the dissociation of MCC. Meanwhile, two other studies have shown that a deubiquitinating enzyme is required for the spindle checkpoint whereas APC/C-dependent ubiquitination is needed for checkpoint inactivation. Collectively, these studies suggest a dynamic model for APC/CCdc20 regulation by MCC in which APC/C- and Mad3-dependent ubiquitination of Cdc20 constitutes a self-regulated switch that rapidly inactivates the spindle checkpoint upon correct chromosome attachment.

Original languageEnglish (US)
Article number23
JournalCell Division
Volume2
DOIs
StatePublished - Jul 24 2007

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Anaphase-Promoting Complex-Cyclosome
Exercise equipment
M Phase Cell Cycle Checkpoints
Ubiquitination
Saccharomycetales
Chromatids
Substrates
Chromosomes
S Phase
Mitosis
Yeast
Dynamic models
Genes
Chemical activation
Switches
Genome
Peptides
Enzymes

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Running on a treadmill : Dynamic inhibition of APC/C by the spindle checkpoint. / Díaz-Martínez, Laura A.; Yu, Hongtao.

In: Cell Division, Vol. 2, 23, 24.07.2007.

Research output: Contribution to journalArticle

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