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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalNature Structural and Molecular Biology
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2019

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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