A role for DNA polymerase alpha in epigenetic control of transcriptional silencing in fission yeast

EMBO J. 2001 Jun 1;20(11):2857-66. doi: 10.1093/emboj/20.11.2857.


In the fission yeast Schizosaccharomyces pombe, transcriptional silencing at the mating-type region, centromeres and telomeres is epigenetically controlled, and results from the assembly of higher order chromatin structures. Chromatin proteins associated with these silenced loci are believed to serve as molecular bookmarks that help promote inheritance of the silenced state during cell division. Specifically, a chromodomain protein Swi6 is believed to be an important determinant of the epigenetic imprint. Here, we show that a mutation in DNA polymerase alpha (pol(alpha)) affects Swi6 localization at the mating-type region and causes a 45-fold increase in spontaneous transition from the silenced epigenetic state to the expressed state. We also demonstrate that pol(alpha) mutant cells are defective in Swi6 localization at centromeres and telomeres. Genetic analysis suggests that Polalpha and Swi6 are part of the same silencing pathway. Interestingly, we found that Swi6 directly binds to Pol(alpha) in vitro. Moreover, silencing-defective mutant Pol(alpha) displays reduced binding to Swi6 protein. This work indicates involvement of a DNA replication protein, Pol(alpha), in heterochromatin assembly and inheritance of epigenetic chromatin structures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Conserved Sequence
  • DNA Polymerase I / chemistry
  • DNA Polymerase I / genetics*
  • DNA Polymerase I / metabolism*
  • Fungal Proteins / chemistry*
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Gene Silencing*
  • Humans
  • Molecular Sequence Data
  • Restriction Mapping
  • Saccharomyces cerevisiae Proteins*
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces / genetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*
  • Transcription, Genetic*


  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Fungal Proteins
  • SWI6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • DNA Polymerase I