%0 Journal Article
%T APC/C-Cdh1-dependent anaphase and telophase progression during mitotic slippage
%A Kazuhiro Toda
%A Kayoko Naito
%A Satoru Mase
%A Masaru Ueno
%A Masahiro Uritani
%A Ayumu Yamamoto
%A Takashi Ushimaru
%J Cell Division
%D 2012
%I BioMed Central
%R 10.1186/1747-1028-7-4
%X Here we describe mitotic slippage in yeast bub2жд mutant cells that are defective in the repression of precocious telophase onset (mitotic exit). Precocious activation of anaphase promoting complex/cyclosome (APC/C)-Cdh1 caused mitotic slippage in the presence of nocodazole, while the SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage, sister-chromatid separation and chromosome missegregation), in addition to telophase onset (mitotic exit), during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C-Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of insufficient kinetochore-microtubule attachments.The sequential activation of APC/C-Cdc20 to APC/C-Cdh1 during mitosis is central to accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre-anaphase) causes mitotic slippage in SAC-activated cells. For the prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in humans.The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that plays a major role in cell cycle control by targeting substrates for proteasomal degradation. The complex is activated by two WD40 activator proteins, Cdc20/Fizzy/Fzy or Cdh1/Fizzy-related/Fzr. This destruction is strictly ordered to ensure that cell cycle events are executed in a timely fashion [1-5]. Whereas APC/C-Cdc20 is activated at metaphase-anaphase transition, APC/C-Cdh1 is activated after APC/C-Cdc20 activation. In the budding yeast Saccharomyces cerevisiae, APC/C-Cdh1 is activated from telophase to late G1 phase [6,7]. The switch from APC/C-Cdc20 to APC/C-Cdh1 is regulated by multiple mechanisms [5,8-10]: Cyclin B-Cdk1 (cyclin-dependent kinase) inhibits Cdh1 activation in metaphase, but cyclin B degradation mediated by APC/C in late M phase reduces cyclin B-Cdk1 acti
%K Anaphase promoting complex/cyclosome (APC/C)
%K Bub2
%K Cdh1
%K mitotic exit network (MEN)
%K mitotic slippage
%K Saccharomyces cerevisiae
%K securin
%U http://www.celldiv.com/content/7/1/4