The involvement of ATP produced via (ADP-Ribose)n in the maintenance of DNA replication apparatus during DNA repair.
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.
Maruta
Hideharu
H
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Okita
Naoyuki
N
Takasawa
Ryoko
R
Uchiumi
Fumiaki
F
Hatano
Tsutomu
T
Tanuma
Sei-ichi
S
D000255:Adenosine Triphosphate / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D011756:Diphosphates / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D013938:Thymidine Monophosphate / Q000494:pharmacology
D001549:Benzamides; D002868:Chromosomal Proteins, Non-Histone; D011756:Diphosphates; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D009243:NAD; C080077:oenothein B; D008769:Methylnitronitrosoguanidine; D011064:Poly Adenosine Diphosphate Ribose; D013938:Thymidine Monophosphate; C025160:3-aminobenzamide; D000255:Adenosine Triphosphate; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase