Lee M Y, Byrnes J J, Downey K M, So A G
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.
利用聚（dA-dT）作为模板，通过哺乳动物DNA聚合酶δ研究了1-β-D-阿拉伯呋喃糖基-ATP（ara-ATP）抑制DNA合成的机制以及6-巯基嘌呤核糖核苷5'-单磷酸（6-MPR-P）对这种抑制作用的增强作用。ara-ATP对DNA合成的抑制作用与ara-AMP掺入聚（dA-dT）有关。最近邻分析表明，ara-AMP并非绝对的链终止剂，而是具有3'-末端阿拉伯糖基核苷酸的链延伸缓慢。添加6-巯基嘌呤的核苷酸衍生物6-巯基嘌呤核糖核苷5'-单磷酸可显著增强ara-ATP对DNA合成的抑制作用。在6-MPR-P存在下，DNA合成抑制作用增强是由于ara-AMP掺入增加。6-MPR-P增加ara-AMP掺入的机制是选择性抑制DNA聚合酶的3'至5'核酸外切酶活性，从而阻止DNA链3'末端新掺入的ara-AMP被去除。
