HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, H. Articles by Goodman, M. F. Search for Related Content PubMed PubMed Citation Articles by Yu, H. Articles by Goodman, M. F. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 268, Issue 21, 15935-15943, 07, 1993

Ionization of bromouracil and fluorouracil stimulates base mispairing frequencies with guanine

H Yu, R Eritja, LB Bloom and MF Goodman
Department of Biological Sciences, University of Southern California, Los Angeles 90089-1340.

To test whether ionized base pairs influence polymerase-catalyzed misinsertion rates, we measured the efficiency of forming 5-bromouracil (B), 5-fluorouracil (F), and thymine base pairs with guanine and adenine as a function of pH using avian myeloblastosis reverse transcriptase. When B, F, and T were present as dNTP substrates, misincorporation efficiencies opposite G, normalized to incorporation of C opposite G, increased by about 20-, 13-, and 7-fold, respectively, as reaction pH increased from 7.0 to 9.5. Incorporation efficiencies to form the correct base pairs, B.A and F.A, normalized to T.A, decreased by 4- and 8-fold, respectively, with increasing pH. The effects of pH on misincorporation efficiencies were about 10-fold greater when B, F, and T were present as template bases. The relative misincorporation efficiencies of G opposite template B, F, and T, normalized to incorporation of A opposite B, F, and T, increased by about 430-, 370-, and 70-fold, respectively, as pH was increased from 6.5 to 9.5, while correct incorporation of A opposite template B and F decreased about 10- fold over the same pH range. Plots depicting incorrect and correct incorporation efficiencies versus pH were fit to a pH titration equation giving the fraction of ionized base as a function of pH. We conclude that avian myeloblastosis reverse transcriptase forms B.G and F.G mispairs in an ionized Watson-Crick conformation in preference to a neutral wobble structure containing favored keto tautomers of B or F. Although participation of disfavored enol tautomers in enzyme-catalyzed base mispair formation cannot be ruled out, the results are inconsistent with the "standard" disfavored tautomer model of mutagenesis. Instead, the data support a model in which ionization of halouracil bases is primarily responsible for B- and F-induced mutagenesis.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. T. Morgan, M. T. Bennett, and A. C. Drohat Excision of 5-Halogenated Uracils by Human Thymine DNA Glycosylase: ROBUST ACTIVITY FOR DNA CONTEXTS OTHER THAN CpG J. Biol. Chem., September 21, 2007; 282(38): 27578 - 27586. [Abstract] [Full Text] [PDF]

				J. Takeshita, J. Byun, T. Q. Nhan, D. K. Pritchard, S. Pennathur, S. M. Schwartz, A. Chait, and J. W. Heinecke Myeloperoxidase Generates 5-Chlorouracil in Human Atherosclerotic Tissue: A POTENTIAL PATHWAY FOR SOMATIC MUTAGENESIS BY MACROPHAGES J. Biol. Chem., February 10, 2006; 281(6): 3096 - 3104. [Abstract] [Full Text] [PDF]

				P. Liu, A. Burdzy, and L. C. Sowers DNA ligases ensure fidelity by interrogating minor groove contacts Nucleic Acids Res., August 24, 2004; 32(15): 4503 - 4511. [Abstract] [Full Text] [PDF]

				J. M. Keith, D. A. E. Cochran, G. H. Lala, P. Adams, D. Bryant, and K. R. Mitchelson Unlocking hidden genomic sequence Nucleic Acids Res., February 18, 2004; 32(3): e35 - e35. [Abstract] [Full Text] [PDF]

				J. P. Henderson, J. Byun, J. Takeshita, and J. W. Heinecke Phagocytes Produce 5-Chlorouracil and 5-Bromouracil, Two Mutagenic Products of Myeloperoxidase, in Human Inflammatory Tissue J. Biol. Chem., June 20, 2003; 278(26): 23522 - 23528. [Abstract] [Full Text] [PDF]

				N. Pariente, A. Airaksinen, and E. Domingo Mutagenesis versus Inhibition in the Efficiency of Extinction of Foot-and-Mouth Disease Virus J. Virol., June 15, 2003; 77(12): 7131 - 7138. [Abstract] [Full Text] [PDF]

				N. Pariente, S. Sierra, P. R. Lowenstein, and E. Domingo Efficient Virus Extinction by Combinations of a Mutagen and Antiviral Inhibitors J. Virol., October 15, 2001; 75(20): 9723 - 9730. [Abstract] [Full Text] [PDF]

				M. Meyers, M. W. Wagner, H.-S. Hwang, T. J. Kinsella, and D. A. Boothman Role of the hMLH1 DNA Mismatch Repair Protein in Fluoropyrimidine-mediated Cell Death and Cell Cycle Responses Cancer Res., July 1, 2001; 61(13): 5193 - 5201. [Abstract] [Full Text] [PDF]

				J. P. Henderson, J. Byun, M. V. Williams, M. L. McCormick, W. C. Parks, L. A. Ridnour, and J. W. Heinecke Bromination of deoxycytidine by eosinophil peroxidase: A mechanism for mutagenesis by oxidative damage of nucleotide precursors PNAS, February 1, 2001; (2001) 41146998. [Abstract] [Full Text]

				S. Sierra, M. Dávila, P. R. Lowenstein, and E. Domingo Response of Foot-and-Mouth Disease Virus to Increased Mutagenesis: Influence of Viral Load and Fitness in Loss of Infectivity J. Virol., September 15, 2000; 74(18): 8316 - 8323. [Abstract] [Full Text]

				H. Terato, A. Masaoka, M. Kobayashi, S. Fukushima, Y. Ohyama, M. Yoshida, and H. Ide Enzymatic Repair of 5-Formyluracil. II. MISMATCH FORMATION BETWEEN 5-FORMYLURACIL AND GUANINE DURING DNA REPLICATION AND ITS RECOGNITION BY TWO PROTEINS INVOLVED IN BASE EXCISION REPAIR (AlkA) AND MISMATCH REPAIR (MutS) J. Biol. Chem., August 27, 1999; 274(35): 25144 - 25150. [Abstract] [Full Text] [PDF]

				A. Masaoka, H. Terato, M. Kobayashi, Y. Ohyama, and H. Ide Oxidation of Thymine to 5-Formyluracil in DNA Promotes Misincorporation of dGMP and Subsequent Elongation of a Mismatched Primer Terminus by DNA Polymerase J. Biol. Chem., May 4, 2001; 276(19): 16501 - 16510. [Abstract] [Full Text] [PDF]

				J. P. Henderson, J. Byun, M. V. Williams, M. L. McCormick, W. C. Parks, L. A. Ridnour, and J. W. Heinecke Bromination of deoxycytidine by eosinophil peroxidase: A mechanism for mutagenesis by oxidative damage of nucleotide precursors PNAS, February 13, 2001; 98(4): 1631 - 1636. [Abstract] [Full Text] [PDF]