PCNA connects DNA replication to epigenetic inheritance in yeast

Zhiguo Zhang, Kei Ichi Shibahara, Bruce Stillman

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Abstract

Formation of a heterochromatin-like structure results in transcriptional silencing at the HM mating-type loci and telomeres in Saccharomyces cerevisiae1-3. 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.

Original languageEnglish (US)
Pages (from-to)221-225
Number of pages5
JournalNature
Volume408
Issue number6809
DOIs
StatePublished - Nov 9 2000

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Zhang, Z., Shibahara, K. I., & Stillman, B. (2000). PCNA connects DNA replication to epigenetic inheritance in yeast. Nature, 408(6809), 221-225. https://doi.org/10.1038/35041601