Reference: Li F, et al. (2019) Apn2 resolves blocked 3' ends and suppresses Top1-induced mutagenesis at genomic rNMP sites. Nat Struct Mol Biol 26(3):155-163

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Abstract


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' ends harboring terminal adducts, such as 2',3'-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-DNA conjugates, terminal 2',3'-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' end blocks and identify a role for APN2 in maintaining genome integrity during rNMP repair.

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Li F, Wang Q, Seol JH, Che J, Lu X, Shim EY, Lee SE, Niu H
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