A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae

Transcriptional silencing in the budding yeast Saccharomyces cerevisiae may be linked to DNA replication and cell cycle progression. In this study, we have surveyed the effect of 41 mutations in genes with a role in replicati on, the cell cycle, and DNA repair on silencing at HMR. Mutations in PCNA ( POL30), RF-C (CDC44), polymerase epsilon (POL2, DPB2, DPB11), and CDC45? we re found to restore silencing at a mutant HMR silencer allele that was stil l a chromosomal origin of replication. Replication timing experiments indic ated that the mutant HMR locus was replicated I;lte in S-phase, at the same time as wild-type HMR. Restoration of silencing by PCNA and CDC45 mutation s required the origin recognition complex binding site of the HMR-E silence r. Several models for the precise role of these replication proteins in sil encing are discussed.