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PMID: 8389438 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cyclobutane thymine dimers in a ras proto-oncogene hot spot activate the gene by point mutation.

Nucleic acids research ·Vol. 21 ·No. 10 ·1993-05-25 ·Pages 2355-61

Kamiya H, Murata N, Murata T, Iwai S, Matsukage A, Masutani C, Hanaoka F, Ohtsuka E

Abstract

ras proto-oncogenes with a cyclobutane-type thymine photodimer (cis-syn or trans-syn isomer) were constructed by replacement of a portion of the gene with a chemically synthesized fragment. When the genes were transfected by the calcium phosphate method into mouse NIH3T3 cells, they induced focus-formation, indicating that both photoproducts were mutagenic in mammalian cells. Sequence analysis of the ras gene fragments derived from the transformed cells showed that the genes were activated by a point mutation. The mutations detected most frequently were 3'-T-->A for the cis-syn isomer and 5'-T-->A for the trans-syn isomer. In contrast, a different trend of mutations was observed when a primer on a DNA template with a cis-syn dimer was extended in vitro by either DNA polymerase beta or alpha.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Base Sequence Chromatography, High Pressure Liquid Cyclobutanes DNA Restriction Enzymes Genes, ras Genetic Vectors Mice Molecular Sequence Data Mutagenesis Oligonucleotides/chemical synthesis Point Mutation Polymerase Chain Reaction Pyrimidine Dimers Transfection
Chemicals
Cyclobutanes Oligonucleotides Pyrimidine Dimers DNA Restriction Enzymes
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kamiya H
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Murata N
Murata T
Iwai S
Matsukage A
Masutani C
Hanaoka F
Ohtsuka E
References (45)
45 references, click to expand
  1. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
    Science. 1988 Jan 29;239(4839):487-91 PMID: 2448875
  2. Mechanisms of ultraviolet-induced mutation. Mutational spectra in the Escherichia coli lacI gene for a wild-type and an excision-repair-deficient strain.
    J Mol Biol. 1987 Nov 20;198(2):187-202 PMID: 2828636
  3. Synthesis of a trans-syn thymine dimer building block. Solid phase synthesis of CGTAT[t,s]TATGC.
    Nucleic Acids Res. 1988 Jun 10;16(11):5123-36 PMID: 3387219
  4. Expression of active rat DNA polymerase beta in Escherichia coli.
    Biochemistry. 1988 Apr 19;27(8):2983-90 PMID: 3042024
  5. DNA repair enzymes.
    Annu Rev Biochem. 1988;57:29-67 PMID: 3052275
  6. Frequency and spectrum of mutations produced by a single cis-syn thymine-thymine cyclobutane dimer in a single-stranded vector.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):8141-5 PMID: 3054882
  7. Activation of N-ras induced by ultraviolet irradiation in vitro.
    Oncogene Res. 1988;3(1):9-20 PMID: 3060800
  8. Establishment and characterization of a melanoma cell line from a xeroderma pigmentosum patient: activation of N-ras at a potential pyrimidine dimer site.
    Cancer Res. 1989 Mar 1;49(5):1229-35 PMID: 2645048
  9. Sequence-specific inhibition of DNA strand elongation by incorporation of 9-beta-D-arabinofuranosyladenine.
    Cancer Res. 1989 Apr 15;49(8):2077-81 PMID: 2467740
  10. Transformation of NIH3T3 cells with synthetic c-Ha-ras genes.
    Jpn J Cancer Res. 1989 Mar;80(3):200-3 PMID: 2542206
  11. DNA primase-DNA polymerase alpha assembly from mouse FM3A cells. Purification of constituting enzymes, reconstitution, and analysis of RNA priming as coupled to DNA synthesis.
    J Biol Chem. 1989 Jun 15;264(17):10065-71 PMID: 2722861
  12. Production of single-stranded DNA templates by exonuclease digestion following the polymerase chain reaction.
    Nucleic Acids Res. 1989 Jul 25;17(14):5865 PMID: 2548171
  13. SOS-dependent replication past a single trans-syn T-T cyclobutane dimer gives a different mutation spectrum and increased error rate compared with replication past this lesion in uninduced cells.
    J Bacteriol. 1990 Apr;172(4):2105-12 PMID: 2180917
  14. cis-syn thymine dimers are not absolute blocks to replication by DNA polymerase I of Escherichia coli in vitro.
    Biochemistry. 1990 Feb 13;29(6):1624-32 PMID: 2185842
  15. Peptide mapping of the four subunits of the mouse DNA polymerase alpha-primase complex.
    Biochem Biophys Res Commun. 1990 Jul 31;170(2):589-95 PMID: 2383257
  16. T-T cyclobutane dimers are misinstructive, rather than non-instructive, mutagenic lesions.
    Mol Gen Genet. 1990 Jun;222(1):166-8 PMID: 2233676
  17. Synthesis and characterization of a substrate for T4 endonuclease V containing a phosphorodithioate linkage at the thymine dimer site.
    Nucleic Acids Res. 1990 Dec 25;18(24):7279-86 PMID: 2259623
  18. 1H NMR assignment and melting temperature study of cis-syn and trans-syn thymine dimer containing duplexes of d(CGTATTATGC).d(GCATAATACG).
    Biochemistry. 1990 Sep 18;29(37):8858-66 PMID: 2271562
  19. Molecular mechanisms of ultraviolet radiation carcinogenesis.
    Photochem Photobiol. 1990 Dec;52(6):1119-36 PMID: 2087500
  20. Transforming activity of a synthetic c-Ha-ras gene containing O6-methylguanine in codon 12.
    Jpn J Cancer Res. 1991 Sep;82(9):997-1002 PMID: 1938604
  21. Induction of mutation of a synthetic c-Ha-ras gene containing hypoxanthine.
    Cancer Res. 1992 Apr 1;52(7):1836-9 PMID: 1551113
  22. A eukaryotic DNA glycosylase/lyase recognizing ultraviolet light-induced pyrimidine dimers.
    Nature. 1992 Apr 23;356(6371):725-8 PMID: 1373868
  23. c-Ha-ras containing 8-hydroxyguanine at codon 12 induces point mutations at the modified and adjacent positions.
    Cancer Res. 1992 Jun 15;52(12):3483-5 PMID: 1596906
  24. An abasic site analogue activates a c-Ha-ras gene by a point mutation at modified and adjacent positions.
    Nucleic Acids Res. 1992 Sep 11;20(17):4409-15 PMID: 1408742
  25. PCNA-induced DNA synthesis past cis-syn and trans-syn-I thymine dimers by calf thymus DNA polymerase delta in vitro.
    Nucleic Acids Res. 1992 Oct 25;20(20):5403-6 PMID: 1359505
  26. In vitro replication study of modified bases in ras sequences.
    Chem Pharm Bull (Tokyo). 1992 Oct;40(10):2792-5 PMID: 1464111
  27. Human-tumor-derived cell lines contain common and different transforming genes.
    Cell. 1981 Dec;27(3 Pt 2):467-76 PMID: 6101201
  28. Pyrimidine dimers in ultraviolet-irradiated DNA's.
    J Mol Biol. 1966 May;17(1):237-54 PMID: 4289765
  29. Characterization of the photodimers from DNA.
    Biochem Biophys Res Commun. 1967 May 5;27(3):384-90 PMID: 6035120
  30. Defective repair replication of DNA in xeroderma pigmentosum.
    Nature. 1968 May 18;218(5142):652-6 PMID: 5655953
  31. Trans-syn thymine dimers in ultraviolet-irradiated denatured DNA: identification and photoreactivability.
    Biochim Biophys Acta. 1968 Aug 23;166(1):9-15 PMID: 4880562
  32. Quantitation of cyclobutane pyrimidine dimer formation in double- and single-stranded DNA fragments of defined sequence.
    Radiat Res. 1982 Jan;89(1):99-112 PMID: 7063608
  33. Specificity of UV mutagenesis in the lac promoter of M13lac hybrid phage DNA.
    Nature. 1982 Jun 17;297(5867):596-8 PMID: 7045681
  34. In vitro bypass of UV-induced lesions by Escherichia coli DNA polymerase I: specificity of nucleotide incorporation.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1541-5 PMID: 6340105
  35. Changes in DNA base sequence induced by targeted mutagenesis of lambda phage by ultraviolet light.
    J Mol Biol. 1984 Mar 5;173(3):273-91 PMID: 6230458
  36. Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity?
    Nature. 1984 Mar 1-7;308(5954):69-72 PMID: 6700714
  37. DNA repair protects against cutaneous and internal neoplasia: evidence from xeroderma pigmentosum.
    Carcinogenesis. 1984 Apr;5(4):511-4 PMID: 6705149
  38. Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient.
    Proc Natl Acad Sci U S A. 1984 Aug;81(15):4771-5 PMID: 6087347
  39. Sequence analysis of ultraviolet-induced mutations in M13lacZ hybrid phage DNA.
    J Mol Biol. 1984 Dec 5;180(2):217-37 PMID: 6439876
  40. Activation of N-ras in a human melanoma cell line.
    Mol Cell Biol. 1985 Mar;5(3):582-5 PMID: 3887133
  41. Mutagenic specificity of ultraviolet light.
    J Mol Biol. 1985 Mar 5;182(1):45-65 PMID: 3923204
  42. Biological and biochemical properties of human rasH genes mutated at codon 61.
    Cell. 1986 Jan 17;44(1):167-76 PMID: 3510078
  43. ras genes.
    Annu Rev Biochem. 1987;56:779-827 PMID: 3304147
  44. Human cancer and cellular oncogenes.
    Biochem J. 1987 Apr 15;243(2):313-27 PMID: 3307760
  45. Overproduction of cellular and activated Ha-ras proteins by mutating a synthetic gene.
    Chem Pharm Bull (Tokyo). 1987 Dec;35(12):4878-82 PMID: 3330471
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/21.10.2355
Published
1993-05-25
Pages
2355-61
Language
English
Region
England
NLM ID
0411011
PMCID
PMC309532
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/21.10.2355 PMC Full Text View journal details
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