Role of PCNA-dependent stimulation of 3′-phosphodiesterase and 3′-5′ exonuclease activities of human Ape2 in repair of oxidative DNA damage

Peter Burkovics, Ildikó Hajdú, Valéria Szukacsov, I. Unk, L. Haracska

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Human Ape2 protein has 3′ phosphodiesterase activity for processing 3′-damaged DNA termini, 3′-5′ exonuclease activity that supports removal of mismatched nucleotides from the 3′-end of DNA, and a somewhat weak AP-endonuclease activity. However, very little is known about the role of Ape2 in DNA repair processes. Here, we examine the effect of interaction of Ape2 with proliferating cell nuclear antigen (PCNA) on its enzymatic activities and on targeting Ape2 to oxidative DNA lesions. We show that PCNA strongly stimulates the 3′-5′ exonuclease and 3′ phosphodiesterase activities of Ape2, but has no effect on its AP-endonuclease activity. Moreover, we find that upon hydrogenperoxide treatment Ape2 redistributes to nuclear foci where it colocalizes with PCNA. In concert with these results, we provide biochemical evidence that Ape2 can reduce the mutagenic consequences of attack by reactive oxygen species not only by repairing 3'-damaged termini but also by removing 3′-end adenine opposite from 8-oxoG. Based on these findings we suggest the involvement of Ape2 in repair of oxidative DNA damage and PCNA-dependent repair synthesis.

Original languageEnglish
Pages (from-to)4247-4255
Number of pages9
JournalNucleic Acids Research
Volume37
Issue number13
DOIs
Publication statusPublished - 2009

Fingerprint

spleen exonuclease
Phosphodiesterase I
Type 5 Cyclic Nucleotide Phosphodiesterases
Proliferating Cell Nuclear Antigen
Human Activities
Exonucleases
DNA Damage
DNA-(Apurinic or Apyrimidinic Site) Lyase
Phosphoric Diester Hydrolases
DNA
Adenine
DNA Repair
Reactive Oxygen Species
Nucleotides

ASJC Scopus subject areas

  • Genetics

Cite this

Role of PCNA-dependent stimulation of 3′-phosphodiesterase and 3′-5′ exonuclease activities of human Ape2 in repair of oxidative DNA damage. / Burkovics, Peter; Hajdú, Ildikó; Szukacsov, Valéria; Unk, I.; Haracska, L.

In: Nucleic Acids Research, Vol. 37, No. 13, 2009, p. 4247-4255.

Research output: Contribution to journalArticle

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