Abstract
In mammalian cells, both semiconservative DNA replication and the DNA repair patch synthesis induced by high doses of ultraviolet radiation are known to be inhibited by aphidicolin, indicating the involvement in these processes of one or both of the aphidicolin-sensitive DNA polymerases, alpha and/or delta. In this paper, N2-(p-n-butylphenyl)-2'-deoxyguanosine-5'-triphosphate, a strong inhibitor of polymerase alpha and a weak inhibitor of polymerase delta, is used to further characterize the DNA polymerase(s) involved in these two forms of nuclear DNA synthesis. In permeable human fibroblasts, DNA replication and ultraviolet-induced DNA repair synthesis are more resistant to the inhibitor than DNA polymerase alpha by factors of approximately 500 and 3000, respectively. These findings are most consistent with the involvement of DNA polymerase delta in these processes.
MeSH Terms
Cells, Cultured
DNA Polymerase II/antagonists & inhibitors
DNA Polymerase III
DNA Repair/drug effects
DNA Replication/drug effects
Deoxyguanine Nucleotides/pharmacology
Humans
Nucleic Acid Synthesis Inhibitors
Ultraviolet Rays
Chemicals
Deoxyguanine Nucleotides
Nucleic Acid Synthesis Inhibitors
N(2)-(4-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate
DNA Polymerase II
DNA Polymerase III
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dresler S L
Frattini M G
References (21)
21 references, click to expand
-
Inhibition of Bacillus subtilis DNA polymerase III by arylhydrazinopyrimidines. Novel properties of 2-thiouracil derivatives.
Biochim Biophys Acta. 1976 Apr 15;432(1):37-48
PMID: 816386
-
Purification and characterization of two new high molecular weight forms of DNA polymerase delta.
Biochemistry. 1986 Jan 14;25(1):26-36
PMID: 3954990
-
Comparison of DNA polymerase alpha and delta from bone marrow.
Biochemistry. 1978 Oct 3;17(20):4226-31
PMID: 708707
-
Rate and extent of DNA repair in nondividing human diploid fibroblasts.
Cancer Res. 1981 Mar;41(3):819-25
PMID: 7459869
-
New views of the biochemistry of eucaryotic DNA replication revealed by aphidicolin, an unusual inhibitor of DNA polymerase alpha.
Cell. 1981 Mar;23(3):647-8
PMID: 6784928
-
DNA polymerase delta: one polypeptide, two activities.
Biochemistry. 1982 May 11;21(10):2513-8
PMID: 6284202
-
Characterization of deoxyribonucleic acid repair synthesis in permeable human fibroblasts.
Biochemistry. 1982 May 11;21(10):2557-64
PMID: 7093202
-
Fidelity of DNA synthesis.
Annu Rev Biochem. 1982;51:429-57
PMID: 6214209
-
Identification of DNA polymerases involved in DNA excision repair in diploid human fibroblasts.
J Biol Chem. 1983 Aug 25;258(16):9990-4
PMID: 6411709
-
Synthesis and characterization of N2-(p-n-butylphenyl)-2'-deoxyguanosine and its 5'-triphosphate and their inhibition of HeLa DNA polymerase alpha.
J Med Chem. 1984 Feb;27(2):175-81
PMID: 6694166
-
Further studies on calf thymus DNA polymerase delta purified to homogeneity by a new procedure.
Biochemistry. 1984 Apr 24;23(9):1906-13
PMID: 6426510
-
On the fidelity of DNA replication. Lack of primer position effect on the fidelity of mammalian DNA polymerases.
J Biol Chem. 1984 Jun 10;259(11):6712-4
PMID: 6233276
-
Butylphenyl dGTP: a selective and potent inhibitor of mammalian DNA polymerase alpha.
Nucleic Acids Res. 1984 Apr 25;12(8):3695-706
PMID: 6728682
-
Comparative enzymology of ultraviolet-induced DNA repair synthesis and semiconservative DNA replication in permeable diploid human fibroblasts.
J Biol Chem. 1984 Nov 25;259(22):13947-52
PMID: 6438087
-
Monoclonal antibodies against human DNA polymerase-alpha inhibit DNA replication in permeabilized human cells.
J Biol Chem. 1985 Jan 10;260(1):134-8
PMID: 3917431
-
Identification of a higher molecular weight DNA polymerase alpha catalytic polypeptide in monkey cells by monoclonal antibody.
Proc Natl Acad Sci U S A. 1984 Dec;81(24):7777-81
PMID: 6393127
-
Differential inhibitors of DNA polymerases alpha and delta.
Biochem Biophys Res Commun. 1985 Oct 30;132(2):628-34
PMID: 4062942
-
Stimulation of deoxyribonucleic acid excision repair in human fibroblasts pretreated with sodium butyrate.
Biochemistry. 1985 Nov 19;24(24):6861-9
PMID: 4074730
-
Differential inhibition of human placental DNA polymerases delta and alpha by BuPdGTP and BuAdATP.
Nucleic Acids Res. 1985 Dec 9;13(23):8623-30
PMID: 3936020
-
Inhibition of DNA replication and DNA polymerase alpha activity by monoclonal anti-(DNA polymerase alpha) immunoglobulin G and F(ab) fragments.
Biochemistry. 1985 Dec 3;24(25):7440-5
PMID: 4084590
-
DNA polymerase-alpha. Purification and structural characterization of the near homogeneous enzyme from human KB cells.
J Biol Chem. 1977 Sep 25;252(18):6528-35
PMID: 893425