RRC ID |
73051
|
著者 |
Bai S, Sun L, Wang X, Wang SM, Luo ZQ, Wang Y, Jin QW.
|
タイトル |
Recovery from spindle checkpoint-mediated arrest requires a novel Dnt1-dependent APC/C activation mechanism.
|
ジャーナル |
PLoS Genet
|
Abstract |
The activated spindle assembly checkpoint (SAC) potently inhibits the anaphase-promoting complex/cyclosome (APC/C) to ensure accurate chromosome segregation at anaphase. Early studies have recognized that the SAC should be silenced within minutes to enable rapid APC/C activation and synchronous segregation of chromosomes once all kinetochores are properly attached, but the underlying silencers are still being elucidated. Here, we report that the timely silencing of SAC in fission yeast requires dnt1+, which causes severe thiabendazole (TBZ) sensitivity and increased rate of lagging chromosomes when deleted. The absence of Dnt1 results in prolonged inhibitory binding of mitotic checkpoint complex (MCC) to APC/C and attenuated protein levels of Slp1Cdc20, consequently slows the degradation of cyclin B and securin, and eventually delays anaphase entry in cells released from SAC activation. Interestingly, Dnt1 physically associates with APC/C upon SAC activation. We propose that this association may fend off excessive and prolonged MCC binding to APC/C and help to maintain Slp1Cdc20 stability. This may allow a subset of APC/C to retain activity, which ensures rapid anaphase onset and mitotic exit once SAC is inactivated. Therefore, our study uncovered a new player in dictating the timing and efficacy of APC/C activation, which is actively required for maintaining cell viability upon recovery from the inhibition of APC/C by spindle checkpoint.
|
巻・号 |
18(9)
|
ページ |
e1010397
|
公開日 |
2022-9-1
|
DOI |
10.1371/journal.pgen.1010397
|
PII |
PGENETICS-D-22-00538
|
PMID |
36108046
|
PMC |
PMC9514617
|
MeSH |
Anaphase-Promoting Complex-Cyclosome / genetics
Anaphase-Promoting Complex-Cyclosome / metabolism
Cdc20 Proteins / genetics
Cdc20 Proteins / metabolism
Cell Cycle Proteins* / genetics
Cell Cycle Proteins* / metabolism
Kinetochores / metabolism
M Phase Cell Cycle Checkpoints / genetics
Securin / genetics
Spindle Apparatus / genetics
Spindle Apparatus / metabolism
Thiabendazole* / metabolism
|
IF |
5.175
|
リソース情報 |
酵母 |
FY13256 (JY774)
FY13257 (JY775) |