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Science 9 February 1996:
Vol. 271. no. 5250, pp. 802 - 805
DOI: 10.1126/science.271.5250.802
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Reports

Mutagenesis in Mammalian Cells Induced by Triple Helix Formation and Transcription-Coupled Repair

Gan Wang,  Michael M. Seidman,  Peter M. Glazer (1)

When mammalian cells were treated with triplex-forming oligonucleotides of sufficient binding affinity, mutations were specifically induced in a simian virus 40 vector contained within the cells. Triplex-induced mutagenesis was not detected in xeroderma pigmentosum group A cells nor in Cockayne's syndrome group B cells, indicating a requirement for excision repair and for transcription-coupled repair, respectively, in the process. Triplex formation was also found to stimulate DNA repair synthesis in human cell extracts, in a pattern correlating with the inhibition of transcription in such extracts. These findings may have implications for therapeutic applications of triplex DNA and raise the possibility that naturally occurring triple helices are a source of genetic instability.


G. Wang and P. M. Glazer, Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040, USA.
M. M. Seidman, OncorPharm, 200 Perry Parkway, Gaithersburg, MD 20877, USA.
(1) To whom correspondence should be addressed.


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J. Biol. Chem. 274, 21763-21768
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Blood 92, 712-736
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Hypermutation of Immunoglobulin Genes in Memory B Cells of DNA Repair-deficient Mice.
H. Jacobs, Y. Fukita, G. T.J. van der Horst, J. de Boer, G. Weeda, J. Essers, N. de Wind, B. P. Engelward, L. Samson, S. Verbeek, et al. (1998)
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Peptide nucleic acid-targeted mutagenesis of a chromosomal gene in mouse cells.
A. F. Faruqi, M. Egholm, and P. M. Glazer (1998)
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The Identification and Characterization of a G4-DNA Resolvase Activity.
C. Harrington, Y. Lan, and S. A. Akman (1997)
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Accessibility of nuclear DNA to triplex-forming oligonucleotides: The integrated HIV-1 provirus as a target.
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PNAS 94, 79-84
   Abstract »    Full Text »    PDF »
Stability of DNA Triplexes on Shuttle Vector Plasmids in the Replication Pool in Mammalian Cells.
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J. Biol. Chem. 275, 39117-39124
   Abstract »    Full Text »    PDF »
Triplex-induced Recombination in Human Cell-free Extracts. DEPENDENCE ON XPA AND HsRad51.
H. J. Datta, P. P. Chan, K. M. Vasquez, R. C. Gupta, and P. M. Glazer (2001)
J. Biol. Chem. 276, 18018-18023
   Abstract »    Full Text »    PDF »
PKD1 Unusual DNA Conformations Are Recognized by Nucleotide Excision Repair.
A. Bacolla, A. Jaworski, T. D. Connors, and R. D. Wells (2001)
J. Biol. Chem. 276, 18597-18604
   Abstract »    Full Text »    PDF »
Targeted Gene Knockout by 2'-O-Aminoethyl Modified Triplex Forming Oligonucleotides.
N. Puri, A. Majumdar, B. Cuenoud, F. Natt, P. Martin, A. Boyd, P. S. Miller, and M. M. Seidman (2001)
J. Biol. Chem. 276, 28991-28998
   Abstract »    Full Text »    PDF »
Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions.
K. M. Vasquez, J. Christensen, L. Li, R. A. Finch, and P. M. Glazer (2002)
PNAS 99, 5848-5853
   Abstract »    Full Text »    PDF »
High-frequency intrachromosomal gene conversion induced by triplex-forming oligonucleotides microinjected into mouse cells.
Z. Luo, M. A. Macris, A. F. Faruqi, and P. M. Glazer (2000)
PNAS 97, 9003-9008
   Abstract »    Full Text »    PDF »


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