title: Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms.
abstract: Srs2 helicase is known to dismantle nucleofilaments of Rad51 recombinase to prevent spurious recombination events and unwind trinucleotide sequences that are prone to hairpin formation. Here we document a new, unexpected genome maintenance role of Srs2 in the suppression of mutations arising from mis-insertion of ribonucleoside monophosphates during DNA replication. In cells lacking RNase H2, Srs2 unwinds DNA from the 5' side of a nick generated by DNA topoisomerase I at a ribonucleoside monophosphate residue. In addition, Srs2 interacts with and enhances the activity of the nuclease Exo1, to generate a DNA gap in preparation for repair. Srs2-Exo1 thus functions in a new pathway of nick processing-gap filling that mediates tolerance of ribonucleoside monophosphates in the genome. Our results have implications for understanding the basis of Aicardi-Goutières syndrome, which stems from inactivation of the human RNase H2 complex.
authors.affiliation: 1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2].
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Potenski
authors.affiliation: 1] Molecular Biophysics and Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [2].
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Molecular Biophysics and Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Klein
mesh_terms: D000818:Animals; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016914:Ribonuclease H / Q000378:metabolism*; D012265:Ribonucleotides / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012265:Ribonucleotides; D029701:Saccharomyces cerevisiae Proteins; C061376:SRS2 protein, S cerevisiae; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; C091139:ribonuclease HII; D016914:Ribonuclease H; D004265:DNA Helicases