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Eukaryotic Cell, December 2004, p. 1627-1638, Vol. 3, No. 6
1535-9778/04/$08.00+0 DOI: 10.1128/EC.3.6.1627-1638.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas
Received 1 April 2004/ Accepted 30 July 2004
How cells determine when to initiate DNA replication is poorly understood. Here we report that in Saccharomyces cerevisiae overexpression of the dosage-dependent cell cycle regulator genes DCR2 (YLR361C) and GID8 (DCR1/YMR135C) accelerates initiation of DNA replication. Cells lacking both GID8 and DCR2 delay initiation of DNA replication. Genetic analysis suggests that Gid8p functions upstream of Dcr2p to promote cell cycle progression. DCR2 is predicted to encode a gene product with phosphoesterase activity. Consistent with these predictions, a DCR2 allele carrying a His338 point mutation, which in known protein phosphatases prevents catalysis but allows substrate binding, antagonized the function of the wild-type DCR2 allele. Finally, we report genetic interactions involving GID8, DCR2, and CLN3 (which encodes a G1 cyclin) or SWI4 (which encodes a transcription factor of the G1/S transcription program). Our findings identify two gene products with a probable regulatory role in the timing of initiation of cell division.
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