PMID: 698189Jul 25, 1978Paper

Biochemistry of terminal deoxynucleotidyltransferase: mechanism of inhibition by adenosine 5'-triphosphate

Biochemistry
M J Modak

Abstract

The polymerization of deoxyribunucleoside triphosphate catalyzed by terminal deoxyribonucleotidyltransferase (TdT, EC 2.7.7.31) is severely inhibited by the addition of ribonucleoside triphosphates, ATP being the most potent inhibitor. Examination of the inhibitory effect of ATP using oligo(dA)12-18 as well as activated DNA as primers revealed that (a) ATP inhibition is not due to its addition onto a 3'-OH primer terminus ad judged by the lack of incorporation of labeled ATP, although under similar conditions incorporation of GTP can be demonstrated, (b) a consistent degree of inhibition was noted independent of primer or enzyme concentration; (c) addition of ATP to an ongoing reaction promptly reduces the rate of polymerization; (d) kinetic studies indicate a competitive (with respect to substrate deoxy triphosphate) pattern of inhibition; (e) addition of excess deoxyribotriphosphate promptly relieves the inhibition. Unlike ATP, other ribotriphosphates yield a mixed pattern of inhibition partly mediated by competitive mechanisms. GTP and CTP and to a minor extent UTP are incorporated into DNA in the presence or absence of deoxy triphosphate. Furthermore, addition of ATP also inhibits incorporation of GTP and CTP.

References

Feb 1, 1977·Nucleic Acids Research·J J Hutton, F J Bollum
Apr 10, 1975·The New England Journal of Medicine·R McCaffreyD Baltimore
Apr 10, 1975·The New England Journal of Medicine·R C Gallo
May 3, 1976·Biochemical and Biophysical Research Communications·S L MarcusM J Modak
Jul 2, 1971·Biochemical and Biophysical Research Communications·L M Chang
Oct 15, 1971·Biochemical and Biophysical Research Communications·R RoychoudhuryH Kössel
Feb 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·R McCaffreyD Baltimore
Jan 1, 1965·Comparative Biochemistry and Physiology·T G BRADY, C I O'DONOVAN

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Citations

Dec 21, 2012·Journal of Virology·Scott A Jones, Jianming Hu
Mar 26, 1998·Biochemical and Biophysical Research Communications·K HanakiH Yoshikura
Jul 15, 2009·Biochimica Et Biophysica Acta·Edward A Motea, Anthony J Berdis
Jul 16, 1980·Biochemical and Biophysical Research Communications·K OnoA Matsukage
Mar 29, 1983·Biochemical and Biophysical Research Communications·M BasuM J Modak
Aug 30, 1983·Biochemistry·L H Breimer
Nov 1, 1986·International Journal of Peptide and Protein Research·N ChandramouliR B Merrifield

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