Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage.
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.
Burkovics
Peter
P
Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged H-6701, Hungary.
Hajdú
Ildikó
I
Szukacsov
Valéria
V
Unk
Ildiko
I
Haracska
Lajos
L
D000225:Adenine / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000032:analysis / Q000378:metabolism*; D004720:Endonucleases; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D064251:Multifunctional Enzymes; D010084:Oxidation-Reduction; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000378:metabolism*
D064251:Multifunctional Enzymes; D018809:Proliferating Cell Nuclear Antigen; D006861:Hydrogen Peroxide; D004720:Endonucleases; D005090:Exodeoxyribonucleases; D010727:Phosphoric Diester Hydrolases; C530688:APEX2 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D000225:Adenine