RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability

Mol Cell. 2011 Dec 23;44(6):978-88. doi: 10.1016/j.molcel.2011.10.017.


Genome instability, a hallmark of cancer progression, is thought to arise through DNA double strand breaks (DSBs). Studies in yeast and mammalian cells have shown that DSBs and instability can occur through RNA:DNA hybrids generated by defects in RNA elongation and splicing. We report that in yeast hybrids naturally form at many loci in wild-type cells, likely due to transcriptional errors, but are removed by two evolutionarily conserved RNase H enzymes. Mutants defective in transcriptional repression, RNA export and RNA degradation show increased hybrid formation and associated genome instability. One mutant, sin3Δ, changes the genome profile of hybrids, enhancing formation at ribosomal DNA. Hybrids likely induce damage in G1, S and G2/M as assayed by Rad52 foci. In summary, RNA:DNA hybrids are a potent source for changing genome structure. By preventing their formation and accumulation, multiple RNA biogenesis factors and RNase H act as guardians of the genome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Chromosomes, Artificial, Yeast / genetics
  • Chromosomes, Artificial, Yeast / metabolism
  • DNA / genetics*
  • Genomic Instability / genetics*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Mutation
  • Nucleic Acid Hybridization
  • RNA / biosynthesis*
  • RNA / genetics*
  • Rad52 DNA Repair and Recombination Protein / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Ribonuclease H / genetics
  • Ribonuclease H / metabolism*
  • Ribonucleases / genetics
  • Ribonucleases / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic


  • RAD52 protein, S cerevisiae
  • Rad52 DNA Repair and Recombination Protein
  • Repressor Proteins
  • SIN3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • RNA
  • DNA
  • Ribonucleases
  • Rnh201 protein, S cerevisiae
  • Ribonuclease H
  • ribonuclease HI
  • Histone Deacetylases