DISTURBANCE OF NORMAL-CELL CYCLE PROGRESSION ENHANCES THE ESTABLISHMENT OF TRANSCRIPTIONAL SILENCING IN SACCHAROMYCES-CEREVISIAE

Previous studies have indicated that mutation of RAP1 (rap1(s)) or of the HMR-E silencer ARS consensus element leads to metastable repressio n of HMR. A number of extragenic suppressor mutations (sds, suppressor s of defective silencing) that increase the fraction of repressed cell s in rap1(s) hmr Delta A strains have been identified. Here we report the cloning of three SBS genes. SDS11 is identical to SWI6, a transcri ptional regulator of genes required for DNA replication and of cyclin genes. SDS12 is identical to RNR1, which encodes a subunit of ribonucl eotide reductase. SDS15 is identical to CIN8, whose product is require d for Spindle formation. We propose that mutations in these genes impr ove the establishment of silencing by interfering with normal cell cyc le progression. In support of this idea, we show that exposure to hydr oxyurea, which increases the length of S phase, also restores silencin g in rap1(s) hmr Delta A strains. Mutations in different cyclin genes (CLN3, CLB5, and CLB2) and two cell cycle transcriptional regulators ( SW14 and MBP1) also suppress the silencing defect at HMR. The effect o f these cell cycle regulators is not specific to the rap1(s) or hmr De lta A mutation, since swi6, swi4, and clb5 mutations also suppress mut ations in SIR1, another gene implicated in the establishment of silenc ing. Several mutations also improve the efficiency of telomeric silenc ing in wild-type strains, further demonstrating that disturbance of th e cell cycle has a general effect on position effect repression in Sac charomyces cerevisiae. We suggest several possible models to explain t his phenomenon.