A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
01 01 2021
01 01 2021
Historique:
received:
08
04
2020
accepted:
17
11
2020
entrez:
1
1
2021
pubmed:
2
1
2021
medline:
12
2
2021
Statut:
ppublish
Résumé
During cell division, kinetochores couple chromosomes to spindle microtubules. To protect against chromosome gain or loss, kinetochores lacking microtubule attachment locally catalyze association of the checkpoint proteins Cdc20 and Mad2, which is the key event in the formation of a diffusible checkpoint complex that prevents mitotic exit. We elucidated the mechanism of kinetochore-catalyzed Mad2-Cdc20 assembly with a probe that specifically monitors this assembly reaction at kinetochores in living cells. We found that catalysis occurs through a tripartite mechanism that includes localized delivery of Mad2 and Cdc20 substrates and two phosphorylation-dependent interactions that geometrically constrain their positions and prime Cdc20 for interaction with Mad2. These results reveal how unattached kinetochores create a signal that ensures genome integrity during cell division.
Identifiants
pubmed: 33384372
pii: 371/6524/64
doi: 10.1126/science.abc1424
pmc: PMC8191211
mid: NIHMS1704860
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Cdc20 Proteins
0
Cell Cycle Proteins
0
FZY-1 protein, C elegans
0
MDF-1 protein, C elegans
0
MDF-2 protein, C elegans
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
bub-1 protein, C elegans
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-67Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM074215
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM104141
Pays : United States
Organisme : NIH HHS
ID : S10 OD021724
Pays : United States
Informations de copyright
Copyright © 2021, American Association for the Advancement of Science.
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