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

Biochemistry. 1980 Jan 8;19(1):215-9. doi: 10.1021/bi00542a032.


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) have been investigated with mammalian DNA polymerase delty 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Arabinonucleotides* / analogs & derivatives
  • Bone Marrow / enzymology
  • DNA / biosynthesis*
  • DNA-Directed DNA Polymerase / metabolism*
  • Inosine Monophosphate / analogs & derivatives
  • Inosine Monophosphate / pharmacology*
  • Inosine Nucleotides / pharmacology*
  • Kinetics
  • Rabbits
  • Substrate Specificity
  • Thionucleotides / pharmacology*
  • Vidarabine Phosphate* / analogs & derivatives


  • Arabinonucleotides
  • Inosine Nucleotides
  • Thionucleotides
  • Vidarabine Phosphate
  • Inosine Monophosphate
  • ara-ATP
  • thioinosinic acid
  • Adenosine Triphosphate
  • DNA
  • DNA-Directed DNA Polymerase