Nucleic Acids Research, 1980, Vol. 8, No. 1 99-110
© 1980
Articles |
Butylanilinouracil: a selective inhibitor of HeLa cell DNA synthesis and HeLa cell DNA polymerase alpha
*Department of Pharmacology, University of Massachusetts Medical School Worcester, MA 01605, USA +Worcester Foundation for Experimental Biology Shrewsbury, MA 01545, USA
Received November 20, 1979.
A series of 6-anilinouracils, dGTP analogues which selectively inhibit specific bacterial DNA polymerases, were examined for their capacity to inhibit purified DNA polymerases from HeLa cells. The p-n-butyl derivative (BuAU) was found to inhibit DNA polymerase
with a Ki of approximately 60 µM. The inhibitory effect of BuAU was reversed specifically by dGTP and was observed only for DNA polymerase
polymerases ß and
were not inhibited by drug at concentrations as high as 1 mM. BuAU also was inhibitory in vivo in HeLa cell culture; at 100 µM it reversibly inhibited cell division and selectively depressed DNA synthesis. The results of these studies indicate that BuAU is an inhibitor with considerable potential as a specific probe with which to dissect the structure of mammalian polymerase
and its putative role in cellular DNA replication.