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

Fuyang Li, Quan Wang, Ja-Hwan Seol, Jun Che, Xiaoyu Lu, Eun Yong Shim, Sang Eun Lee, Hengyao Niu

Nature structural & molecular biology 2019 Mar

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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.

Citation

Fuyang Li, Quan Wang, Ja-Hwan Seol, Jun Che, Xiaoyu Lu, Eun Yong Shim, Sang Eun Lee, Hengyao Niu. Apn2 resolves blocked 3' ends and suppresses Top1-induced mutagenesis at genomic rNMP sites. Nature structural & molecular biology. 2019 Mar;26(3):155-163