PCNA connects DNA replication to epigenetic inheritance in yeast

Formation of a heterochromatin-like structure results in transcriptional si lencing at the HM mating-type loci and telomeres in Saccharomyces cerevisia e(1-3). Once formed, such epigenetically determined structures are inherite d for many mitotic divisions(4). Here we show that mutations in the prolife rating cell nuclear antigen (PCNA), an essential component at the DNA repli cation fork(5), reduced repression of genes near a telomere and at the sile nt mating-type locus, HMR. The pol30-8 mutant displayed coexistence of both repressed (pink) and de-repressed (white) cells within a single colony whe n assayed with the ADE2 gene inserted at HMR. Unlike pol30-8, the pol30-6 a nd pol30-79 mutants partially reduced gene silencing at telomeres and the H MR and synergistically decreased silencing in cells lacking chromatin assem bly factor 1 (CAF-1). All silencing defective mutants showed reduced bindin g to CAF-1 in vitro and altered chromatin association of the CAF-1 large su bunit in vivo. Thus, PCNA participates in inheritance of both DNA and epige netic chromatin structures during the S phase of the cell cycle, the latter by at least two mechanisms.