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)