MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bouchard, J.
Right arrow Articles by Momparler, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bouchard, J.
Right arrow Articles by Momparler, R. L.

Incorporation of 5-Aza-2'-deoxycytidine-5'-triphosphate into DNA. Interactions with mammalian DNA polymerase alpha and DNA methylase

J Bouchard and RL Momparler

In order to understand further the molecular mode of action of 5-Aza-2'- deoxycytidine (5-AZA-dCyd), a potent antileukemic agent, we prepared enzymatically 5-Aza-2'-deoxycytidine 5'-triphosphate (5-AZA-dCTP) and performed studies with purified DNA polymerase alpha and DNA methylase from mammalian cells. DNA polymerase alpha catalyzed the incorporation of 5-AZA-dCTP into DNA. The apparent Km value for 5-AZA-dCTP was estimated to be 3.0 microM; the Km of dCTP was 2.0 microM. The apparent Vmax of 5-AZA-dCTP was slightly lower than that for dCTP. 5-AZA-dCTP was a weak competitive inhibitor (Ki 4.3 microM) with respect to dCTP. Template studies with 5-AZA-dCTP showed that this nucleotide analogue was incorporated into poly(dIC), but not into poly(dAT), suggesting that the incorporation follows the rules of Watson-Crick base pairing. Incorporation of 5-AZA-dCTP into hemimethylated DNA produced a significant inhibition of DNA methylase. These results show that 5-AZA- dCTP is a very good substrate for DNA polymerase alpha and that its incorporation into DNA inhibits DNA methylation.

Volume 24, Issue 1, pp. 109-114, 07/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Egger, S. Jeong, S. G. Escobar, C. C. Cortez, T. W. H. Li, Y. Saito, C. B. Yoo, P. A. Jones, and G. Liang
Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival
PNAS, September 19, 2006; 103(38): 14080 - 14085.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
J. R Kuykendall
5-Azacytidine and Decitabine Monotherapies of Myelodysplastic Disorders
Ann. Pharmacother., October 1, 2005; 39(10): 1700 - 1708.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
K. N. Bhalla
Epigenetic and Chromatin Modifiers As Targeted Therapy of Hematologic Malignancies
J. Clin. Oncol., June 10, 2005; 23(17): 3971 - 3993.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Matsubayashi, N. Sato, N. Fukushima, C. J. Yeo, K. M. Walter, K. Brune, F. Sahin, R. H. Hruban, and M. Goggins
Methylation of Cyclin D2 Is Observed Frequently in Pancreatic Cancer but Is Also an Age-related Phenomenon in Gastrointestinal Tissues
Clin. Cancer Res., April 1, 2003; 9(4): 1446 - 1452.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
J. Goffin and E. Eisenhauer
DNA methyltransferase inhibitors--state of the art
Ann. Onc., November 1, 2002; 13(11): 1699 - 1716.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1983 by the American Society for Pharmacology and Experimental Therapeutics