BUBR1 and closed MAD2 (C-MAD2) interact directly to assemble a functional mitotic checkpoint complex.

ABSTRACT: The mitotic checkpoint maintains genomic stability by ensuring that chromosomes are accurately segregated during mitosis. When the checkpoint is activated, the mitotic checkpoint complex (MCC), assembled from BUBR1, BUB3, CDC20, and MAD2, directly binds and inhibits the anaphase-promoting complex/cyclosome (APC/C) until all chromosomes are properly attached and aligned. The mechanisms underlying MCC assembly and MCC-APC/C interaction are not well characterized. Here, we show that a novel interaction between BUBR1 and closed MAD2 (C-MAD2) is essential for MCC-mediated inhibition of APC/C. Intriguingly, Arg(133) and Gln(134) in C-MAD2 are required for BUBR1 interaction. The same residues are also critical for MAD2 dimerization and MAD2 binding to p31(comet), a mitotic checkpoint silencing pr

SUBMITTER: Tipton AR 

PROVIDER: S-EPMC3122179 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature