Gid8p (Dcr1p) and Dcr2p function in a common pathway to promote START completion in Saccharomyces cerevisiae.
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 G(1) cyclin) or SWI4 (which encodes a transcription factor of the G(1)/S transcription program). Our findings identify two gene products with a probable regulatory role in the timing of initiation of cell division.
Pathak
Ritu
R
Department of Biochemistry and Biophysics, Texas A and M University, 2128 TAMU, College Station, TX 77843, USA.
Bogomolnaya
Lydia M
LM
Guo
Jinbai
J
Polymenis
Michael
M
D000483:Alleles; D002453:Cell Cycle; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006868:Hydrolysis; D015151:Immunoblotting; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic
D017931:DNA Primers; C501513:Gid8 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA; C501514:Dcr2 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases; D005947:Glucose