Mechanism of Inhibition of Deoxyribonucleic Acid Synthesis by 1-β-D-Arabinofuranosyladenosine Triphosphate and its Potentiation by 6-Mercaptopurine Ribonucleoside 5'-Monophosphate

Marietta Y.W.Tsang Lee, John J. Byrnes, Kathleen M. Downey, G. So Antero

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The mechanism of inhibition of DNA synthesis by 1-β-D-arabinofuranosyl-ATP (ara-ATP) and the potentiation of this inhibition by 6-mercaptopurine ribonucleoside 5'-monophosphate (6-MPR-P) have been investigated with mammalian DNA polymerase by using poly(dA-dT) as the template. The inhibition of DNA synthesis by ara-ATP correlates with incorporation of ara-AMP into poly(dA-dT). Nearest-neighbor analysis indicates that ara-AMP does not act as an absolute chain terminator but rather that chains with 3'-terminal arabinosyl nucleotides are extended slowly. The inhibition of DNA synthesis by ara-ATP is markedly enhanced by the addition of the nucleotide derivative of 6-mercaptopurine, 6-mercaptopurine ribonucleoside 5'-monophosphate. The increased inhibition of DNA synthesis in the presence of 6-MPR-P is due to increased incorporation of ara-AMP. The mechanism by which 6-MPR-P increases the incorporation of ara-AMP is by selective inhibition of the 3' to 5' exonuclease activity of DNA polymerase, thereby preventing the removal of newly incorporated ara-AMP at 3' termini of DNA chains.

Original languageEnglish (US)
Pages (from-to)215-219
Number of pages5
JournalBiochemistry
Volume19
Issue number1
DOIs
StatePublished - Jan 1 1980

ASJC Scopus subject areas

  • Biochemistry

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