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Apn2 resolves blocked 3' ends and suppresses Top1-induced mutagenesis at genomic rNMP sites.

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.

SUBMITTER: Li F 

PROVIDER: S-EPMC6515903 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Apn2 resolves blocked 3' ends and suppresses Top1-induced mutagenesis at genomic rNMP sites.

Li Fuyang F   Wang Quan Q   Seol Ja-Hwan JH   Che Jun J   Lu Xiaoyu X   Shim Eun Yong EY   Lee Sang Eun SE   Niu Hengyao H  

Nature structural & molecular biology 20190218 3

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 ge  ...[more]

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