Rif1 binds to G quadruplexes and suppresses replication over long distances

Nat Struct Mol Biol. 2015 Nov;22(11):889-97. doi: 10.1038/nsmb.3102. Epub 2015 Oct 5.

Abstract

Rif1 regulates replication timing and repair of double-strand DNA breaks. Using a chromatin immunoprecipitation-sequencing method, we identified 35 high-affinity Rif1-binding sites in fission yeast chromosomes. Binding sites tended to be located near dormant origins and to contain at least two copies of a conserved motif, CNWWGTGGGGG. Base substitution within these motifs resulted in complete loss of Rif1 binding and in activation of late-firing or dormant origins located up to 50 kb away. We show that Rif1-binding sites adopt G quadruplex-like structures in vitro, in a manner dependent on the conserved sequence and on other G tracts, and that purified Rif1 preferentially binds to this structure. These results suggest that Rif1 recognizes and binds G quadruplex-like structures at selected intergenic regions, thus generating local chromatin structures that may exert long-range suppressive effects on origin firing.

MeSH terms

  • Binding Sites
  • DNA Replication*
  • DNA, Fungal / chemistry
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism
  • G-Quadruplexes*
  • Molecular Sequence Data
  • Protein Binding
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / physiology*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Analysis, DNA
  • Telomere-Binding Proteins / metabolism*

Substances

  • DNA, Fungal
  • Rif1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Telomere-Binding Proteins

Associated data

  • GEO/GSE28182
  • GEO/GSE34369
  • GEO/GSE65293