Open AccessButylanilinouracil: a selective inhibitor of HeLa cell DNA synthesis and HeLa cell DNA polymerase alpha
Author(s) -
George E. Wright,
Earl F. Baril,
Neal C. Brown
Publication year - 1980
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/8.1.99
Subject(s) - dna polymerase , biology , dna polymerase ii , microbiology and biotechnology , hela , dna synthesis , dna clamp , polymerase , dna replication , dna , dna polymerase i , dna polymerase mu , biochemistry , primer (cosmetics) , cell , polymerase chain reaction , circular bacterial chromosome , gene , reverse transcriptase , chemistry , organic chemistry
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.
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