PCNA connects DNA replication to epigenetic inheritance in yeast

Abstract

Formation of a heterochromatin-like structure results in transcriptional silencing at the HM mating-type loci and telomeres in Saccharomyces cerevisiae^1,2,3. Once formed, such epigenetically determined structures are inherited for many mitotic divisions⁴. Here we show that mutations in the proliferating cell nuclear antigen (PCNA), an essential component at the DNA replication fork⁵, reduced repression of genes near a telomere and at the silent mating-type locus, HMR. The pol30-8 mutant displayed coexistence of both repressed (pink) and de-repressed (white) cells within a single colony when assayed with the ADE2 gene inserted at HMR. Unlike pol30-8, the pol30-6 and pol30-79 mutants partially reduced gene silencing at telomeres and the HMR and synergistically decreased silencing in cells lacking chromatin assembly factor 1 (CAF-1). All silencing defective mutants showed reduced binding to CAF-1 in vitro and altered chromatin association of the CAF-1 large subunit in vivo. Thus, PCNA participates in inheritance of both DNA and epigenetic chromatin structures during the S phase of the cell cycle, the latter by at least two mechanisms.