Butylanilinouracil: a selective inhibitor of HeLa cell DNA synthesis and HeLa cell DNA polymerase alpha

Nucleic Acids Res. 1980 Jan 11;8(1):99-109. doi: 10.1093/nar/8.1.99.


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 microM. The inhibitory effect of BuAU was reversed specifically by dGTP and was observed only for DNA polymerase alpha; polymerases beta and lambda were not inhibited by drug at concentrations as high as 1 mM. BuAU also was inhibitory in vivo in HeLa cell culture; at 100 microM 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.

Publication types

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

MeSH terms

  • Avian Myeloblastosis Virus / enzymology
  • Bacillus subtilis / enzymology
  • DNA Polymerase I / metabolism
  • DNA Polymerase II / antagonists & inhibitors*
  • DNA Polymerase III / metabolism
  • DNA Replication / drug effects
  • DNA, Neoplasm / biosynthesis*
  • Escherichia coli / enzymology
  • HeLa Cells / drug effects
  • HeLa Cells / metabolism*
  • Humans
  • Kinetics
  • Nucleic Acid Synthesis Inhibitors*
  • RNA-Directed DNA Polymerase / metabolism
  • Structure-Activity Relationship
  • Uracil / analogs & derivatives*
  • Uracil / pharmacology


  • DNA, Neoplasm
  • Nucleic Acid Synthesis Inhibitors
  • Uracil
  • butylanilinouracil
  • RNA-Directed DNA Polymerase
  • DNA Polymerase I
  • DNA Polymerase II
  • DNA Polymerase III