TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC

Dong Hyun Kim, Joo Seok Han, Peter Ly, Qiaozhen Ye, Moira A. McMahon, Kyungjae Myung, Kevin D. Corbett, Don W. Cleveland

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The mitotic checkpoint ensures accurate chromosome segregation through assembly of the mitotic checkpoint complex (MCC), a soluble inhibitor of the anaphase-promoting complex/cyclosome (APC/C) produced by unattached kinetochores. MCC is also assembled during interphase by Mad1/Mad2 bound at nuclear pores, thereby preventing premature mitotic exit prior to kinetochore maturation and checkpoint activation. Using degron tagging to rapidly deplete the AAA+ ATPase TRIP13, we show that its catalytic activity is required to maintain a pool of open-state Mad2 for MCC assembly, thereby supporting mitotic checkpoint activation, but is also required for timely mitotic exit through catalytic disassembly of MCC. Strikingly, combining TRIP13 depletion with elimination of APC15-dependent Cdc20 ubiquitination/degradation results in a complete inability to exit mitosis, even when MCC assembly at unattached kinetochores is prevented. Thus, mitotic exit requires MCC produced either in interphase or mitosis to be disassembled by TRIP13-catalyzed removal of Mad2 or APC15-driven ubiquitination/degradation of its Cdc20 subunit.

Original languageEnglish (US)
Article number4354
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

Fingerprint

M Phase Cell Cycle Checkpoints
Kinetochores
Interphase
mitosis
assembly
Chemical activation
Anaphase-Promoting Complex-Cyclosome
Degradation
activation
Chromosomes
degradation
Adenosine Triphosphatases
Ubiquitination
chromosomes
Catalyst activity
Mitosis
inhibitors
marking
catalytic activity
elimination

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC. / Kim, Dong Hyun; Han, Joo Seok; Ly, Peter; Ye, Qiaozhen; McMahon, Moira A.; Myung, Kyungjae; Corbett, Kevin D.; Cleveland, Don W.

In: Nature communications, Vol. 9, No. 1, 4354, 01.12.2018.

Research output: Contribution to journalArticle

Kim, Dong Hyun ; Han, Joo Seok ; Ly, Peter ; Ye, Qiaozhen ; McMahon, Moira A. ; Myung, Kyungjae ; Corbett, Kevin D. ; Cleveland, Don W. / TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC. In: Nature communications. 2018 ; Vol. 9, No. 1.
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