APHIDICOLIN INHIBITS DNA-SYNTHESIS BY DNA-POLYMERASE ALPHA AND ISOLATED-NUCLEI BY A SIMILAR MECHANISM
APHIDICOLIN INHIBITS DNA-SYNTHESIS BY DNA-POLYMERASE ALPHA AND ISOLATED-NUCLEI BY A SIMILAR MECHANISM
复制标题
DOI：
10.1093/nar/9.18.4709
复制
发表时间：
1981-01-01
影响因子：
14.9
通讯作者：
KROKAN, RH
中科院分区：
文献类型：
--
作者：
KROKAN, H;WIST, E;KROKAN, RH
Aphidicolin是DNA聚合酶α的选择性抑制剂。与早期报道相反，发现该药物通过类似的机制抑制DNA聚合酶α催化的DNA合成和分离的HeLa细胞核。对于这两种系统，阿非迪霉素主要与dCTP掺入竞争。然而，在相对低浓度的阿非迪霉素下，dCTP掺入的表观Vmax降低50-60%，因此抑制机制是复杂的。此外，在阿非迪霉素存在下观察到dTTP的表观Km增加2-5倍，但dATP和dGTP的表观Km值基本上不变。这与其他证据一起表明，阿非迪霉素的作用机制涉及与dCMP掺入的强烈竞争，与dTMP掺入的较弱竞争，以及与dGMP和dAMP掺入的非常小的竞争（如果有的话）。
Aphidicolin is a selective inhibitor of DNA polymerase α. In contrast to earlier reports, the drug was found to inhibit DNA synthesis catalyzed by DNA polymerase α and isolated HeLa cell nuclei by a similar mechanism. For both systems aphidicolin primarily competed with dCTP incorporation. However, the apparent Vmaxfor dCTP incorporation was reduced by 50-60% at relatively low concentrations of aphidicolin, thus the mechanism of inhibition is complex. Furthermore, a 2-5 fold increase in apparent Kmfor dTTP was observed in the presence of aphidicolin, but the apparent Kmvalues for dATP and dGTP were essentially unaltered. This, together with additional evidence, suggested that the mechanism of action of aphidicolin involves a strong competition with dCMP incorporation, a weaker competition with dTMP incorporation and very little, if any, competition with dGMP and dAMP incorporation.