Unknown

Dataset Information

0

Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding.


ABSTRACT: Premature anaphase onset is prevented by the mitotic checkpoint through production of a "wait anaphase" inhibitor(s) that blocks recognition of cyclin B and securin by Cdc20-activated APC/C, an E3 ubiquitin ligase that targets them for destruction. Using physiologically relevant levels of Mad2, Bub3, BubR1, and Cdc20, we demonstrate that unattached kinetochores on purified chromosomes catalytically generate a diffusible Cdc20 inhibitor or inhibit Cdc20 already bound to APC/C. Furthermore, the chromosome-produced inhibitor requires both recruitment of Mad2 by Mad1 that is stably bound at unattached kinetochores and dimerization-competent Mad2. We show that purified chromosomes promote BubR1 binding to APC/C-Cdc20 by acting directly on Mad2, but not BubR1. Our results support a model in which immobilized Mad1/Mad2 at kinetochores provides a template for initial assembly of Mad2 bound to Cdc20 that is then converted to a final mitotic checkpoint inhibitor with Cdc20 bound to BubR1.

PROVIDER: S-EPMC2655205 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC5268738 | BioStudies
| S-EPMC2173820 | BioStudies
| S-EPMC3713096 | BioStudies
| S-EPMC5949338 | BioStudies
| S-EPMC3947552 | BioStudies
| S-EPMC2897573 | BioStudies
| S-EPMC4210015 | BioStudies
| S-EPMC4773433 | BioStudies
| S-EPMC6195577 | BioStudies
| S-EPMC3998811 | BioStudies