%0 Journal Article
%T Apn2 resolves blocked 3¡ä ends and suppresses Top1-induced mutagenesis at genomic rNMP sites
%J -
%D 2019
%R https://doi.org/10.1038/s41594-019-0186-1
%X Ribonucleoside monophosphates (rNMPs) mis-incorporated during DNA replication are removed by RNase H2-dependent excision repair or by topoisomerase I (Top1)-catalyzed cleavage. The cleavage of rNMPs by Top1 produces 3¡ä ends harboring terminal adducts, such as 2¡ä,3¡ä-cyclic phosphate or Top1 cleavage complex (Top1cc), and leads to frequent mutagenesis and DNA damage checkpoint induction. We surveyed a range of candidate enzymes from Saccharomyces cerevisiae for potential roles in Top1-dependent genomic rNMP removal. Genetic and biochemical analyses reveal that Apn2 resolves phosphotyrosine¨CDNA conjugates, terminal 2¡ä,3¡ä-cyclic phosphates, and their hydrolyzed products. APN2 also suppresses 2-base pair (bp) slippage mutagenesis in RNH201-deficient cells. Our results define additional activities of Apn2 in resolving a wide range of 3¡ä end blocks and identify a role for Apn2 in maintaining genome integrity during rNMP repair
%U https://www.nature.com/articles/s41594-019-0186-1