3′-phosphodiesterase and 3′ → 5′ exonuclease activities of yeast Apn2 protein and requirement of these activities for repair of oxidative DNA damage

I. Unk, L. Haracska, S. Prakash, L. Prakash

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

In Saccharomyces cerevisiae, the AP endonucleases encoded by the APN1 and APN2 genes provide alternate pathways for the removal of abasic sites. Oxidative DNA-damaging agents, such as H2O2, produce DNA strand breaks which contain 3′-phosphate or 3′-phosphoglycolate termini. Such 3′ termini are inhibitory to synthesis by DNA polymerases. Here, we show that purified yeast Apn2 protein contains 3′-phosphodiesterase and 3′ → 5′ exonuclease activities, and mutation of the active-site residue Glu59 to Ala in Apn2 inactivates both these activities. Consistent with these biochemical observations, genetic studies indicate the involvement of APN2 in the repair of H2O2-induced DNA damage in a pathway alternate to APN1, and the Ala59 mutation inactivates this function of Apn2. From these results, we conclude that the ability of Apn2 to remove 3′-end groups from DNA is paramount for the repair of strand breaks arising from the reaction of DNA with reactive oxygen species.

Original languageEnglish (US)
Pages (from-to)1656-1661
Number of pages6
JournalMolecular and cellular biology
Volume21
Issue number5
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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