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. 1987 Mar;84(5):1286–1289. doi: 10.1073/pnas.84.5.1286

Poly(ADP-ribose) may signal changing metabolic conditions to the chromatin of mammalian cells.

P Loetscher, R Alvarez-Gonzalez, F R Althaus
PMCID: PMC304412  PMID: 3103132

Abstract

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.

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Selected References

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  1. Althaus F. R., Lawrence S. D., He Y. Z., Sattler G. L., Tsukada Y., Pitot H. C. Effects of altered [ADP-ribose]n metabolism on expression of fetal functions by adult hepatocytes. Nature. 1982 Nov 25;300(5890):366–368. doi: 10.1038/300366a0. [DOI] [PubMed] [Google Scholar]
  2. Althaus F. R., Lawrence S. D., Sattler G. L., Pitot H. C. ADP-ribosyltransferase activity in cultured hepatocytes. Interactions with DNA repair. J Biol Chem. 1982 May 25;257(10):5528–5535. [PubMed] [Google Scholar]
  3. Alvarez-Gonzalez R., Eichenberger R., Loetscher P., Althaus F. R. A new highly selective physicochemical assay to measure NAD+ in intact cells. Anal Biochem. 1986 Aug 1;156(2):473–480. doi: 10.1016/0003-2697(86)90281-2. [DOI] [PubMed] [Google Scholar]
  4. Aubin R. J., Fréchette A., de Murcia G., Mandel P., Lord A., Grondin G., Poirier G. G. Correlation between endogenous nucleosomal hyper(ADP-ribosyl)ation of histone H1 and the induction of chromatin relaxation. EMBO J. 1983;2(10):1685–1693. doi: 10.1002/j.1460-2075.1983.tb01643.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bauer P. I., Hakam A., Kun E. Mechanisms of poly(ADP-ribose) polymerase catalysis; mono-ADP-ribosylation of poly(ADP-ribose) polymerase at nanomolar concentrations of NAD. FEBS Lett. 1986 Jan 20;195(1-2):331–338. doi: 10.1016/0014-5793(86)80188-0. [DOI] [PubMed] [Google Scholar]
  6. Berger N. A. Poly(ADP-ribose) in the cellular response to DNA damage. Radiat Res. 1985 Jan;101(1):4–15. [PubMed] [Google Scholar]
  7. Butt T. R., Smulson M. Relationship between nicotinamide adenine dinucleotide concentration and in vitro synthesis of poly(adenosine diphosphate ribose) on purified nucleosomes. Biochemistry. 1980 Nov 11;19(23):5235–5242. doi: 10.1021/bi00564a013. [DOI] [PubMed] [Google Scholar]
  8. Farzaneh F., Zalin R., Brill D., Shall S. DNA strand breaks and ADP-ribosyl transferase activation during cell differentiation. Nature. 1982 Nov 25;300(5890):362–366. doi: 10.1038/300362a0. [DOI] [PubMed] [Google Scholar]
  9. Gaal J. C., Pearson C. K. Eukaryotic nuclear ADP-ribosylation reactions. Biochem J. 1985 Aug 15;230(1):1–18. doi: 10.1042/bj2300001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huletsky A., Niedergang C., Fréchette A., Aubin R., Gaudreau A., Poirier G. G. Sequential ADP-ribosylation pattern of nucleosomal histones. ADP-ribosylation of nucleosomal histones. Eur J Biochem. 1985 Jan 15;146(2):277–285. doi: 10.1111/j.1432-1033.1985.tb08650.x. [DOI] [PubMed] [Google Scholar]
  11. Jackowski G., Kun E. Age-dependent variation of rates of polyadenosine-diphosphoribose synthesis by cardiocyte nuclei and the lack of correlation of enzymatic activity with macromolecular size distribution of DNA. J Biol Chem. 1981 Apr 25;256(8):3667–3670. [PubMed] [Google Scholar]
  12. Jacobson M. K., Payne D. M., Alvarez-Gonzalez R., Juarez-Salinas H., Sims J. L., Jacobson E. L. Determination of in vivo levels of polymeric and monomeric ADP-ribose by fluorescence methods. Methods Enzymol. 1984;106:483–494. doi: 10.1016/0076-6879(84)06052-3. [DOI] [PubMed] [Google Scholar]
  13. Juarez-Salinas H., Sims J. L., Jacobson M. K. Poly(ADP-ribose) levels in carcinogen-treated cells. Nature. 1979 Dec 13;282(5740):740–741. doi: 10.1038/282740a0. [DOI] [PubMed] [Google Scholar]
  14. Kawaichi M., Ueda K., Hayaishi O. Multiple autopoly(ADP-ribosyl)ation of rat liver poly(ADP-ribose) synthetase. Mode of modification and properties of automodified synthetase. J Biol Chem. 1981 Sep 25;256(18):9483–9489. [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Labarca C., Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980 Mar 1;102(2):344–352. doi: 10.1016/0003-2697(80)90165-7. [DOI] [PubMed] [Google Scholar]
  17. Loud A. V. A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells. J Cell Biol. 1968 Apr;37(1):27–46. doi: 10.1083/jcb.37.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mandel K. G., Lively M. K., Lombardi D., Amos H. Reactivation of NAD(H) biosynthetic pathway by exogenous NAD+ in Nil cells severely depleted of NAD(H). J Cell Physiol. 1983 Feb;114(2):235–244. doi: 10.1002/jcp.1041140214. [DOI] [PubMed] [Google Scholar]
  19. Paine A. J., Hockin L. J. Effect of hepatocyte culture conditions on their content of nicotinamide coenzymes [proceedings]. Biochem Soc Trans. 1980 Apr;8(2):183–184. doi: 10.1042/bst0080183. [DOI] [PubMed] [Google Scholar]
  20. Sugiura M., Fram R., Munroe D., Kufe D. DNA strand scission and ADP-ribosyltransferase activity during murine erythroleukemia cell differentiation. Dev Biol. 1984 Aug;104(2):484–488. doi: 10.1016/0012-1606(84)90105-2. [DOI] [PubMed] [Google Scholar]
  21. Ueda K., Hayaishi O. ADP-ribosylation. Annu Rev Biochem. 1985;54:73–100. doi: 10.1146/annurev.bi.54.070185.000445. [DOI] [PubMed] [Google Scholar]

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