Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites

Robert E. Johnson, Carlos A. Torres-Ramos, Tadahide Izumi, Sankar Mitra, Satya Prakash, Louise Prakash

Research output: Contribution to journalArticle

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Abstract

Abasic (AP) sites arise in DNA through spontaneous base loss and enzymatic removal of damaged bases. APN1 encodes the major AP-endonuclease of Saccharomyces cerevisiae. Human HAP1 (REF1) encodes the major AP endonuclease which, in addition to its role in DNA repair, functions as a redox regulatory protein. We identify APN2, the yeast homolog of HAP1 and provide evidence that Apn1 and Apn2 represent alternate pathways for repairing AP sites. The apn1Δ apn2Δ strain displays a highly elevated level of MMS-induced mutagenesis, which is dependent on the REV3, REV7, and REV1 genes. Our findings indicate that AP sites are highly cytotoxic and mutagenic in eukaryotes, and that the REV3, REV7-encoded DNA polymerase ζ mediates the mutagenic bypass of AP sites.

Original languageEnglish (US)
Pages (from-to)3137-3143
Number of pages7
JournalGenes and Development
Volume12
Issue number19
DOIs
StatePublished - Oct 1 1998

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Keywords

  • APN1
  • APN2
  • Base excision repair
  • Mutagenic bypass
  • Yeast

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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