title: A saccharomyces cerevisiae RNase H2 interaction network functions to suppress genome instability.
abstract: Errors during DNA replication are one likely cause of gross chromosomal rearrangements (GCRs). Here, we analyze the role of RNase H2, which functions to process Okazaki fragments, degrade transcription intermediates, and repair misincorporated ribonucleotides, in preventing genome instability. The results demonstrate that rnh203 mutations result in a weak mutator phenotype and cause growth defects and synergistic increases in GCR rates when combined with mutations affecting other DNA metabolism pathways, including homologous recombination (HR), sister chromatid HR, resolution of branched HR intermediates, postreplication repair, sumoylation in response to DNA damage, and chromatin assembly. In some cases, a mutation in RAD51 or TOP1 suppressed the increased GCR rates and/or the growth defects of rnh203Δ double mutants. This analysis suggests that cells with RNase H2 defects have increased levels of DNA damage and depend on other pathways of DNA metabolism to overcome the deleterious effects of this DNA damage.
authors.affiliation: Ludwig Institute for Cancer Research, University of California School of Medicine, San Diego, La Jolla, California, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Allen
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Martinez
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Putnam
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kolodner
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics / Q000276:immunology; D016914:Ribonuclease H / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C091139:ribonuclease HII; D016914:Ribonuclease H