Poly(ADP-ribose) catabolism in mammalian cells exposed to DNA-damaging agents.
DNA damage inflicted by the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine, or by UV254nm, stimulated the catabolism of protein-bound poly(ADP-ribose) in the chromatin of cultured hepatocytes. The stimulation was highest at the largest doses of DNA-damaging treatment. As a consequence, the half-life of ADP-ribosyl polymers may drop to less than 41 s. This rapid turnover contrasts with the slow catabolism of a constitutive fraction of polymers exhibiting a half-life of 7.7 h. Our data suggest that post-incisional stimulation of poly(ADP-ribose) biosynthesis in DNA-excision repair is coupled with an adaptation of poly(ADP-ribose) catabolism in mammalian cells.
University of Zürich-Tierspital, Institute of Pharmacology and Biochemistry, Switzerland.
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Alvarez-Gonzalez
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Althaus
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism* / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014466:Ultraviolet Rays
D001549:Benzamides; D002843:Chromatin; D009702:Nucleoside Diphosphate Sugars; D011838:Radiation-Sensitizing Agents; D008769:Methylnitronitrosoguanidine; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide