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

• Published in: Nucleic acids research Vol. 37; no. 13; pp. 4247 - 4255
• Main Authors: Burkovics, Peter, Hajdú, Ildikó, Szukacsov, Valéria, Unk, Ildiko, Haracska, Lajos
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-07-2009; Oxford Publishing Limited (England)
• Subjects: Adenine - metabolism; DNA Damage; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase - analysis; DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism; Exodeoxyribonucleases - metabolism; Genome Integrity, Repair and; Humans; Hydrogen Peroxide - pharmacology; Oxidation-Reduction; Phosphoric Diester Hydrolases - metabolism; Proliferating Cell Nuclear Antigen - analysis; Proliferating Cell Nuclear Antigen - metabolism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkp357

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 hydrogen-peroxide 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.