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 Shim, Sang Lee, Hengyao Niu

Research output: Contribution to journalArticle

1 Citation (Scopus)

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)
JournalNature Structural and Molecular Biology
DOIs
StatePublished - Jan 1 2019

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Ribonucleosides
Mutagenesis
Phosphates
Type I DNA Topoisomerase
Ribonucleases
DNA Replication
Base Pairing
DNA Repair
DNA Damage
Saccharomyces cerevisiae
Molecular Biology
Genome
Enzymes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Apn2 resolves blocked 3′ ends and suppresses Top1-induced mutagenesis at genomic rNMP sites. / Li, Fuyang; Wang, Quan; Seol, Ja Hwan; Che, Jun; Lu, Xiaoyu; Shim, Eun; Lee, Sang; Niu, Hengyao.

In: Nature Structural and Molecular Biology, 01.01.2019.

Research output: Contribution to journalArticle

Li, Fuyang ; Wang, Quan ; Seol, Ja Hwan ; Che, Jun ; Lu, Xiaoyu ; Shim, Eun ; Lee, Sang ; Niu, Hengyao. / Apn2 resolves blocked 3′ ends and suppresses Top1-induced mutagenesis at genomic rNMP sites. In: Nature Structural and Molecular Biology. 2019.
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