Abstract
Nicotinamide was found to be a potent inhibitor of DNA methylation in vivo without interfering with protein or DNA synthesis. The inhibition of DNA methylation in a phage-infected cell resulted in a parallel decrease in the production of viable virus particles. In vitro experiments revealed that nicotinamide inhibits DNA methylase activity in a competitive fashion with respect to S-adenosylmethionine and non-competitively with respect to DNA. These results were interpreted to mean that DNA methylation is an essential step in the process of maturation of the bacteriophage phichi174.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arber W., Linn S. DNA modification and restriction. Annu Rev Biochem. 1969;38:467–500. doi: 10.1146/annurev.bi.38.070169.002343. [DOI] [PubMed] [Google Scholar]
- Buch L., Streeter D., Halpern R. M., Simon L. N., Stout M. G., Smith R. A. Inhibition of transfer ribonucleic acid methylase activity from several human tumors by nicotinamide and nicotinamide analogs. Biochemistry. 1972 Feb 1;11(3):393–397. doi: 10.1021/bi00753a015. [DOI] [PubMed] [Google Scholar]
- Edgell M. H., Hutchison C. A., 3rd, Sinsheimer R. L. The process of infection with bacteriophage phi-X174. 28. Removal of the spike proteins from the phage capsid. J Mol Biol. 1969 Jun 28;42(3):547–557. doi: 10.1016/0022-2836(69)90242-3. [DOI] [PubMed] [Google Scholar]
- Fujimoto D., Srinivasan P. R., Borek E. On the nature of the deoxyribonucleic acid methylases. Biological evidence for the multiple nature of the enzymes. Biochemistry. 1965 Dec;4(12):2849–2855. doi: 10.1021/bi00888a041. [DOI] [PubMed] [Google Scholar]
- Gross H. J., Wildenauer D. Enzymatic methylations. II. In vitro inhibition of tRNA and protein methylation by nicotinamide and isonicotinic acid hydrazide: activation of a s-adenosylmethionine-splitting enzyme in rat liver. Biochem Biophys Res Commun. 1972 Jul 11;48(1):58–64. doi: 10.1016/0006-291x(72)90343-9. [DOI] [PubMed] [Google Scholar]
- Halpern R. M., Chaney S. Q., Halpern B. C., Smith R. A. Nicotinamide: a natural inhibitor of tRNA methylase. Biochem Biophys Res Commun. 1971 Feb 19;42(4):602–607. doi: 10.1016/0006-291x(71)90530-4. [DOI] [PubMed] [Google Scholar]
- Knippers R., Razin A., Davis R., Sinsheimer R. L. The process of infection with Bacteriophage phi-X174. XXIX. In vivo studies on the synthesis of the single-stranded DNA of progeny phi-X174 bacteriophage. J Mol Biol. 1969 Oct 28;45(2):237–263. doi: 10.1016/0022-2836(69)90103-x. [DOI] [PubMed] [Google Scholar]
- Lee A. S., Sinsheimer R. L. Location of the 5-methylcytosine group on the bacteriophage phi X174 genome. J Virol. 1974 Oct;14(4):872–877. doi: 10.1128/jvi.14.4.872-877.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lombardini J. B., Chou T. C., Talalay P. Regulatory properties of adenosine triphosphate-L-methionine S-adenosyltransferase of rat liver. Biochem J. 1973 Sep;135(1):43–57. doi: 10.1042/bj1350043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marinus M. G., Morris N. R. Isolation of deoxyribonucleic acid methylase mutants of Escherichia coli K-12. J Bacteriol. 1973 Jun;114(3):1143–1150. doi: 10.1128/jb.114.3.1143-1150.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Razin A. DNA methylase induced by bacteriophage phiX174. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3773–3775. doi: 10.1073/pnas.70.12.3773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Razin A., Sedat J. W., Sinsheimer R. L. In vivo methylation of replicating bacteriophage phi chi174 DNA. J Mol Biol. 1973 Aug 15;78(3):417–425. doi: 10.1016/0022-2836(73)90465-8. [DOI] [PubMed] [Google Scholar]
- Razin A., Sedat J. W., Sinsheimer R. L. Structure of the DNA of bacteriophage phiX174. VII. Methylation. J Mol Biol. 1970 Oct 28;53(2):251–259. doi: 10.1016/0022-2836(70)90298-6. [DOI] [PubMed] [Google Scholar]
- SINSHEIMER R. L., STARMAN B., NAGLER C., GUTHRIE S. The process of infection with bacteriophage phi-XI74. I. Evidence for a "replicative form". J Mol Biol. 1962 Mar;4:142–160. doi: 10.1016/s0022-2836(62)80047-3. [DOI] [PubMed] [Google Scholar]
- Seydel J. K., Wempe E., Miller G. H., Miller L. Kinetics and mechanisms of action of trimethoprim and sulfonamides, alone or in combination, upon Escherichia coli. Chemotherapy. 1972;17(4):217–258. doi: 10.1159/000220857. [DOI] [PubMed] [Google Scholar]