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PMID: 2987791 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

DNA polymerase alpha and models for proofreading.

Nucleic acids research ·Vol. 13 ·No. 1 ·1985-01-11 ·Pages 261-74

Abbotts J, Loeb LA

Abstract

Using a modified system to measure fidelity at an amber site in phi X174, we have employed DNA polymerase alpha to test different mechanisms for proofreading. DNA polymerase alpha does not exhibit the characteristics of "kinetic proofreading" seen with procaryotic polymerases. Polymerase alpha shows no evidence for a "next nucleotide" effect, and added deoxynucleoside monophosphates do not alter fidelity. Pyrophosphate, which increases error rates with a procaryotic polymerase, appears to weakly improve polymerase alpha fidelity. DNA polymerase alpha does exhibit a dramatic increase in error rate in the presence of a deoxycytidine thiotriphosphate (dCTP alpha S), but this enhanced mutagenesis also occurs under conditions where kinetic proofreading should be otherwise defeated. This particular effect with dCTP alpha S appears specific for DNA polymerase alpha and is not seen with the other polymerases tested.

MeSH Terms
Animals Cattle DNA/genetics DNA Polymerase I/metabolism DNA Polymerase II/metabolism Diphosphates/pharmacology Escherichia coli/enzymology,genetics Models, Chemical Nucleic Acid Hybridization Nucleotides/pharmacology
Chemicals
Diphosphates Nucleotides DNA DNA Polymerase I DNA Polymerase II
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Abbotts J
Loeb L A
References (23)
23 references, click to expand
  1. Fidelity of DNA synthesis.
    Annu Rev Biochem. 1982;51:429-57 PMID: 6214209
  2. Deoxynucleoside [1-thio]triphosphates prevent proofreading during in vitro DNA synthesis.
    Proc Natl Acad Sci U S A. 1981 Nov;78(11):6734-8 PMID: 6458818
  3. A mammalian DNA polymerase alpha holoenzyme functioning on defined in vivo-like templates.
    EMBO J. 1982;1(12):1513-9 PMID: 6765199
  4. 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
  5. Enzymatic synthesis of deoxyribonucleic acid. XXVI. Physical and chemical studies of a homogeneous deoxyribonucleic acid polymerase.
    J Biol Chem. 1969 Jun 10;244(11):2996-3008 PMID: 4890762
  6. The mechanism of Escherichia coli deoxyribonucleic acid polymerase I. Magnetic resonance and kinetic studies of the role of metals.
    J Biol Chem. 1972 Nov 10;247(21):6784-94 PMID: 4343158
  7. A comparison of associated enzyme activities in various deoxyribonucleic acid polymerases.
    J Biol Chem. 1973 May 25;248(10):3398-404 PMID: 4349863
  8. The occurrence of multiple activities in the high-molecular-weight DNA polymerase fraction of mammalian tissues. A preliminary study of some of their properties.
    Eur J Biochem. 1974 Apr 16;43(3):487-99 PMID: 4545528
  9. The infidelity of avian myeloblastosis virus deoxyribonucleic acid polymerase in polynucleotide replication.
    J Biol Chem. 1974 Jul 10;249(13):4086-93 PMID: 4137275
  10. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity.
    Proc Natl Acad Sci U S A. 1974 Oct;71(10):4135-9 PMID: 4530290
  11. In vitro concersion of a calf thymus 8S DNA polymerase to a 7.3S species.
    Nature. 1975 May 29;255(5507):420-2 PMID: 1128705
  12. Kinetic amplification of enzyme discrimination.
    Biochimie. 1975;57(5):587-95 PMID: 1182215
  13. Conformation of deoxynucleoside triphosphate substrates on DNA polymerase I from Escherichia coli as determined by nuclear magnetic relaxation.
    J Biol Chem. 1975 Dec 10;250(23):8913-20 PMID: 1104609
  14. Novikoff hepatoma deoxyribonucleic acid polymerase. Purification and properties of a homogeneous beta polymerase.
    Biochemistry. 1976 Jul 13;15(14):3114-21 PMID: 182203
  15. Incorporation of phosphorothioate groups into fd and phi X174 DNA.
    Biochemistry. 1977 Aug 9;16(16):3633-40 PMID: 329875
  16. Mutagenesis during in vitro DNA synthesis.
    Proc Natl Acad Sci U S A. 1978 Apr;75(4):1924-8 PMID: 347450
  17. Enzymological characterization of DNA polymerase alpha. Basic catalytic properties processivity, and gap utilization of the homogeneous enzyme from human KB cells.
    J Biol Chem. 1979 Jul 10;254(13):6128-37 PMID: 447699
  18. The energy relay: a proofreading scheme based on dynamic cooperativity and lacking all characteristic symptoms of kinetic proofreading in DNA replication and protein synthesis.
    Proc Natl Acad Sci U S A. 1980 Sep;77(9):5248-52 PMID: 6933556
  19. Studies on the inhibition of highly purified calf thymus 8S and 7.3S DNA polymerase alpha by aphidicolin.
    Nucleic Acids Res. 1981 Jan 10;9(1):161-8 PMID: 6782551
  20. On the fidelity of DNA replication. Nucleoside monophosphate generation during polymerization.
    J Biol Chem. 1981 Apr 25;256(8):3978-87 PMID: 7012147
  21. Fidelity of mammalian DNA polymerases.
    Science. 1981 Aug 14;213(4509):765-7 PMID: 6454965
  22. On the fidelity of DNA replication. Effect of the next nucleotide on proofreading.
    J Biol Chem. 1981 Oct 10;256(19):9883-9 PMID: 6456268
  23. Mammalian mutator mutant with an aphidicolin-resistant DNA polymerase alpha.
    Proc Natl Acad Sci U S A. 1983 Feb;80(3):797-801 PMID: 6402775
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
Published
1985-01-11
Pages
261-74
Language
English
Region
England
NLM ID
0411011
PMCID
PMC340989
Subset
IM
Grants
NIA NIH HHS · AG 00057 · United States
NCI NIH HHS · CA 24845 · United States
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