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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

George E. Wright*, Earl F. Baril+ and Neal C. Brown*

*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 {alpha} with a Ki of approximately 60 µM. The inhibitory effect of BuAU was reversed specifically by dGTP and was observed only for DNA polymerase {alpha} polymerases ß and {gamma} 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 {alpha} and its putative role in cellular DNA replication.


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