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Journal of Bacteriology, November 1998, p. 5712-5717, Vol. 180, No. 21
0021-9193/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Examination of the Role of DNA Polymerase Proofreading in the Mutator Effect of Miscoding tRNAs

Malgorzata M. Slupska, Angela G. King, Louise I. Lu, Rose H. Lin, Emily F. Mao, Chantal A. Lackey, Ju-Huei Chiang, Claudia Baikalov, and Jeffrey H. Miller*

Department of Microbiology and Molecular Genetics and Molecular Biology Institute, University of California, Los Angeles, California 90095

Received 2 December 1997/Accepted 26 August 1998

We previously described Escherichia coli mutator tRNAs that insert glycine in place of aspartic acid and postulated that the elevated mutation rate results from generating a mutator polymerase. We suggested that the proofreading subunit of polymerase III, varepsilon , is a likely target for the aspartic acid-to-glycine change that leads to a lowered fidelity of replication, since the altered varepsilon  subunits resulting from this substitution (approximately 1% of the time) are sufficient to create a mutator effect, based on several observations of mutD alleles. In the present work, we extended the study of specific mutD alleles and constructed 16 altered mutD genes by replacing each aspartic acid codon, in series, with a glycine codon in the dnaQ gene that encodes varepsilon . We show that three of these genes confer a strong mutator effect. We have also looked for new mutator tRNAs and have found one: a glycine tRNA that inserts glycine at histidine codons. We then replaced each of the seven histidine codons in the mutD gene with glycine codons and found that in two cases, a strong mutator phenotype results. These findings are consistent with the varepsilon  subunit playing a major role in the mutator effect of misreading tRNAs.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics and the Molecular Biology Institute, University of California, Los Angeles, CA 90095. Phone: (310) 825-8460. Fax: (310) 206-3088. E-mail: jhmiller{at}mbi.ucla.edu.

Journal of Bacteriology, November 1998, p. 5712-5717, Vol. 180, No. 21
0021-9193/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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