DNA strand breaks, NAD metabolism, and programmed cell death.
An intimate relationship exists between DNA single-strand breaks, NAD metabolism, and cell viability in quiescent human lymphocytes. Under steady-state conditions, resting lymphocytes continually break and rejoin DNA. The balanced DNA excision-repair process is accompanied by a proportional consumption of NAD for poly(ADP-ribose) synthesis. However, lymphocytes have a limited capacity to resynthesize NAD from nicotinamide. An increase in DNA strand break formation in lymphocytes, or a block in DNA repair, accelerates poly(ADP-ribose) formation and may induce lethal NAD and ATP depletion. In this way, the level of DNA single-strand breaks in the lymphocyte nucleus is linked to the metabolic activity of the cytoplasm. The programmed removal of lymphocytes (and perhaps of other cells) with damaged DNA, may represent a novel physiologic function for poly(ADP-ribose)-dependent NAD cycling.
D016590:Aphidicolin; D002470:Cell Survival; D004247:DNA / Q000032:analysis* / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004224:Diterpenes / Q000494:pharmacology; D006801:Humans; D007107:Immune System / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*; D009536:Niacinamide / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
D004224:Diterpenes; D009243:NAD; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; D016590:Aphidicolin; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases