Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms

作者：Potenski Catherine J; Niu Hengyao; Sung Patrick^*; Klein Hannah L

来源：Nature, 2014, 511(7508): 251-+.

DOI：10.1038/nature13292

Srs2 helicase is known to dismantle nucleofilaments of Rad51 recombinase to prevent spurious recombination events(1-6) and unwind trinucleotide sequences that are prone to hairpin formation(7). 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-8 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-Goutieres syndrome, which stems from inactivation of the human RNase H2 complex(9).

• 出版日期2014-7-10