Open AccessA Cds1-Mediated Checkpoint Protects the MBF Activator Rep2 from Ubiquitination by Anaphase-Promoting Complex/Cyclosome-Ste9 at S-Phase Arrest in Fission Yeast
Author(s) -
Zhaoqing Chu,
Majid Eshaghi,
Suk Yean Poon,
Jianhua Liu
Publication year - 2009
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00562-09
Subject(s) - schizosaccharomyces pombe , biology , microbiology and biotechnology , ubiquitin ligase , cell cycle checkpoint , cell cycle , phosphorylation , anaphase promoting complex , ubiquitin , activator (genetics) , g2 m dna damage checkpoint , cdc20 , cullin , schizosaccharomyces , transcription factor , anaphase , biochemistry , gene , saccharomyces cerevisiae
Transcription of the MluI cell cycle box (MCB) motif-containing genes at G1 phase is regulated by the MCB-binding factors (MBF) (also called DSC1) inSchizosaccharomyces pombe . Upon S-phase arrest, the MBF transcriptional activity is induced through the accumulation of the MBF activator Rep2. In this study, we show that the turnover of Rep2 is attributable to ubiquitin-mediated proteolysis. Levels of Rep2 oscillate during the cell cycle, with a peak at G1 phase, coincident with the MBF activity. Furthermore, we show that Rep2 ubiquitination requires the function of the E3 ligase anaphase-promoting complex/cyclosome (APC/C). Ste9 can be phosphorylated by the checkpoint kinase Cds1 in vitro, and its inhibition/phosphorylation at S-phase arrest is dependent on the function of Cds1. Our data indicate that the Cds1-dependent stabilization of Rep2 is achieved through the inhibition/phosphorylation of APC/C-Ste9 at the onset of S-phase arrest. Stabilization of Rep2 is important for stimulating transcription of the MBF-dependent genes to ensure a sufficient supply of proteins essential for cell recovery from S-phase arrest. We propose that oscillation of Rep2 plays a role in regulation of periodic transcription of the MBF-dependent genes during cell cycle progression.