Pivotal roles of PCNA loading and unloading in heterochromatin function

Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):E2030-E2039. doi: 10.1073/pnas.1721573115. Epub 2018 Feb 13.

Abstract

In Saccharomyces cerevisiae, heterochromatin structures required for transcriptional silencing of the HML and HMR loci are duplicated in coordination with passing DNA replication forks. Despite major reorganization of chromatin structure, the heterochromatic, transcriptionally silent states of HML and HMR are successfully maintained throughout S-phase. Mutations of specific components of the replisome diminish the capacity to maintain silencing of HML and HMR through replication. Similarly, mutations in histone chaperones involved in replication-coupled nucleosome assembly reduce gene silencing. Bridging these observations, we determined that the proliferating cell nuclear antigen (PCNA) unloading activity of Elg1 was important for coordinating DNA replication forks with the process of replication-coupled nucleosome assembly to maintain silencing of HML and HMR through S-phase. Collectively, these data identified a mechanism by which chromatin reassembly is coordinated with DNA replication to maintain silencing through S-phase.

Keywords: CAF-1; Elg1; PCNA; heterochromatin; nucleosome assembly.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism
  • DNA Replication
  • Gene Deletion
  • Gene Expression Regulation, Fungal*
  • Gene Silencing
  • Genome, Fungal
  • Heterochromatin / metabolism*
  • Histones / metabolism
  • Open Reading Frames
  • Plasmids / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Ribonucleases / metabolism
  • S Phase
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • Elg1 protein, S cerevisiae
  • Heterochromatin
  • Histones
  • POL30 protein, S cerevisiae
  • Proliferating Cell Nuclear Antigen
  • Saccharomyces cerevisiae Proteins
  • Ribonucleases
  • POP2 protein, S cerevisiae