Title: Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms.
Authors: Potenski, Catherine J; Niu, Hengyao; Sung, Patrick; Klein, Hannah L
Published In Nature, (2014 Jul 10)
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.
PubMed ID: 24896181
MeSH Terms: Animals; Cell Line; DNA Damage/genetics; DNA Helicases/genetics; DNA Helicases/metabolism*; Escherichia coli/genetics; Exodeoxyribonucleases/genetics; Exodeoxyribonucleases/metabolism*; Genomic Instability/genetics*; Mutation/genetics*; Ribonuclease H/metabolism*; Ribonucleotides/metabolism*; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism*; Saccharomyces cerevisiae/enzymology*; Saccharomyces cerevisiae/genetics*