MUTATIONS IN THE HOMOLOGOUS ZDS1 AND ZDS2 GENES AFFECT CELL-CYCLE PROGRESSION

The Saccharomyces cerevisiae ZDS1 and ZDS2 genes mere identified as mu lticopy suppressors in distinct genetic screens but were found to enco de highly similar proteins, We show that at semipermissive temperature s, a yeast strain with a cdc28-1N allele was uniquely deficient in pla smid maintenance in comparison with strains harboring other cdc28 ther molabile alleles, Quantitative analysis of plasmid loss rates in cdc28 -IN strains carrying plasmids with multiple replication origins sugges ts that a defect in initiating DNA replication probably causes this pl asmid loss phenotype. The ZDS2 gene was isolated as a multicopy suppre ssor of the cdc28-1N plasmid loss defect. A zds1 deletion exhibits gen etic interactions with cdc28-1N but not with other cdc28 alleles, SIN4 encodes a protein which is part of the RNA polymerase II holoenzyme-m ediator complex, and a sin4 null mutation has pleiotropic effects sugg esting roles in transcriptional regulation and chromatin structure. Th e ZDS2 gene mas isolated as a multicopy suppressor of the temperature- sensitive growth defect caused by the sin4 null mutation. Disruption o f either ZDS1 or ZDS2 causes only modest phenotypes. However, a strain with both ZDS1 and ZDS2 disrupted is extremely slowly growing, has ma rked defects in bud morphology, and shows defects in completing S phas e or entering mitosis.