Mechanism of inhibition of deoxyribonucleic acid synthesis by 1-.beta.-D-arabinofuranosyladenosine triphosphate and its potentiation by 6-mercaptopurine ribonucleoside 5'-monophosphate

Publisher Website
Google Scholar
Abstract
The mechanism of inhibition of DNA synthesis by 1-.beta.-D-arabinofuranosyl-ATP (ara-ATP) and the potentiation of this inhibition by 6-mercaptopurine ribonucleoside 5''-monophosphate (6-MPR-P) were investigated with mammalian DNA polymerase .delta. 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 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 6-MPR-P. 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.

This publication has 1 reference indexed in Scilit: