title: RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute/Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Lamia
authors.initials: L
authors.lastname: Wahba
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Amon
authors.forename: Douglas
authors.initials: D
authors.lastname: Koshland
authors.forename: Milena
authors.initials: M
authors.lastname: Vuica-Ross
mesh_terms: D002453:Cell Cycle; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics*; D051721:Rad52 DNA Repair and Recombination Protein / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016914:Ribonuclease H / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D004247:DNA; D012260:Ribonucleases; C569437:Rnh201 protein, S cerevisiae; D016914:Ribonuclease H; C078856:ribonuclease HI; D006655:Histone Deacetylases