Poly(ADP-ribose) may signal changing metabolic conditions to the chromatin of mammalian cells.
In mammalian cells, NAD+ serves a dual role as a respiratory coenzyme and as a substrate for the posttranslational poly(ADP-ribose) modification of chromatin proteins, catalyzed by the nuclear enzyme poly(ADP-ribose) polymerase [NAD+ ADP-ribosyltransferase, EC 2.4.2.30]. Biological evidence strongly suggests that poly(ADP-ribosyl)ation modulates chromatin functions, although the precise molecular mechanisms involved have not yet been elucidated. Here we describe conditions for the rapid uptake of exogenously supplied NAD+ by living hepatocytes in primary monolayer culture. Raising the intracellular NAD+ concentration by 70% caused a 5-fold increase of chromatin-bound poly(ADP-ribose). We conclude that the constitutive level of posttranslational poly(ADP-ribose) modifications of chromatin proteins in mammalian cells is related to the availability of NAD+, which varies in different physiological and pathological states. We propose that poly-(ADP-ribose) may serve a hitherto unrecognized function by signaling altered metabolic conditions to the chromatin and thus modulate its functions in tune with changing metabolic states.
D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000378:metabolism; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D011919:Rats, Inbred Strains
D002843:Chromatin; D009698:Nucleoproteins; D009702:Nucleoside Diphosphate Sugars; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases