Biological & Pharmaceutical Bulletin 2007-03-01

The involvement of ATP produced via (ADP-Ribose)n in the maintenance of DNA replication apparatus during DNA repair.

Hideharu Maruta, Naoyuki Okita, Ryoko Takasawa, Fumiaki Uchiumi, Tsutomu Hatano, Sei-ichi Tanuma

Index: Biol. Pharm. Bull. 30(3) , 447-50, (2007)

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Abstract

The formation of ATP produced from poly(ADP-ribose) [(ADP-R)n] has been suggested to be required to repair damaged DNA. Here we investigate whether this ATP is involved in DNA replication processes during DNA repair. Poly(ADP-ribosyl)ated mid-S phase cell nuclei, which were isolated from synchronized HeLa S3 cells followed by the treatment with a DNA damaging agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), were revealed to retain DNA replication synthesizing activity during preincubation for de-poly(ADP-ribosyl)ation only in the presence of pyrophosphate (PPi) before DNA synthesis was started by adding 3 mM ATP. This DNA replication activity was not maintained in the presence of a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase (PARG), Oenothein B (Oen B) during the preincubation with PPi. In the preincubation with PPi, muM orders of ATP was produced from (ADP-R)n. These results point to an important function of ATP generated from (ADP-R)n in nuclei for the maintenance of replication apparatus during DNA repair.