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Molecular and Cellular Biology, September 2009, p. 4959-4970, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00562-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Cds1-Mediated Checkpoint Protects the MBF Activator Rep2 from Ubiquitination by Anaphase-Promoting Complex/Cyclosome-Ste9 at S-Phase Arrest in Fission Yeast{triangledown} ,{dagger}

Zhaoqing Chu,1 Majid Eshaghi,1 Suk Yean Poon,1 and Jianhua Liu1,2*

Systems Biology, Genome Institute of Singapore, Biopolis, Singapore 138672,1 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore2

Received 30 April 2009/ Returned for modification 15 June 2009/ Accepted 2 July 2009

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) in Schizosaccharomyces 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.

* Corresponding author. Mailing address: Systems Biology, Genome Institute of Singapore, A*STAR, Biopolis, Singapore 138672, Singapore. Phone: (65) 6478-8123. Fax: (65) 6478-9003. E-mail: liujh{at}gis.a-star.edu.sg

{triangledown} Published ahead of print on 13 July 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, September 2009, p. 4959-4970, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00562-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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