This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Klapacz, J.
Right arrow Articles by Bhagwat, A. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Klapacz, J.
Right arrow Articles by Bhagwat, A. S.

 Previous Article  |  Next Article 

Journal of Bacteriology, December 2002, p. 6866-6872, Vol. 184, No. 24
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.24.6866-6872.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Transcription-Dependent Increase in Multiple Classes of Base Substitution Mutations in Escherichia coli

Joanna Klapacz and Ashok S. Bhagwat*

Department of Chemistry, Wayne State University, Detroit, Michigan 48202

Received 6 May 2002/ Accepted 11 September 2002

We showed previously that transcription in Escherichia coli promotes C · G-to-T · A transitions due to increased deamination of cytosines to uracils in the nontranscribed but not the transcribed strand (A. Beletskii and A. S. Bhagwat, Proc. Natl. Acad. Sci. USA 93:13919-13924, 1996). To study mutations other than that of C to T, we developed a new genetic assay that selects only base substitution mutations and additionally excludes C · G to T · A transitions. This novel genetic reversion system is based on mutations in a termination codon and involves positive selection for resistance to bleomycin or kanamycin. Using this genetic system, we show here that transcription from a strong promoter increases the level of non-C-to-T as well as C-to-T mutations. We find that high-level transcription increases the level of non-C-to-T mutations in DNA repair-proficient cells in three different sequence contexts in two genes and that the rate of mutation is higher by a factor of 2 to 4 under these conditions. These increases are not caused by a growth advantage for the revertants and are restricted to genes that are induced for transcription. In particular, high levels of transcription do not create a general mutator phenotype in E. coli. Sequence analysis of the revertants revealed that the frequency of several different base substitutions increased upon transcription of the bleomycin resistance gene and that G · C-to-T · A transversions dominated the spectrum in cells transcribing the gene. These results suggest that high levels of transcription promote many different spontaneous base substitutions in E. coli.

* Corresponding author. Mailing address: Wayne State University, 463 Chemistry Building, Detroit, MI 48202. Phone: (313) 577-2547. Fax: (313) 577-8822. E-mail: axb{at}chem.wayne.edu.

Journal of Bacteriology, December 2002, p. 6866-6872, Vol. 184, No. 24
0021-9193/02/$04.00+0     DOI: 10.1128/JB.184.24.6866-6872.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shen, H. M., Poirier, M. G., Allen, M. J., North, J., Lal, R., Widom, J., Storb, U. (2009). The activation-induced cytidine deaminase (AID) efficiently targets DNA in nucleosomes but only during transcription. JEM 206: 1057-1071 [Abstract] [Full Text]  
  • Lind, P. A., Andersson, D. I. (2008). Whole-genome mutational biases in bacteria. Proc. Natl. Acad. Sci. USA 105: 17878-17883 [Abstract] [Full Text]  
  • Morton, B. R., Wright, S. I. (2007). Selective Constraints on Codon Usage of Nuclear Genes from Arabidopsis thaliana. Mol Biol Evol 24: 122-129 [Abstract] [Full Text]  
  • Hirsh, A. E., Fraser, H. B., Wall, D. P. (2005). Adjusting for Selection on Synonymous Sites in Estimates of Evolutionary Distance. Mol Biol Evol 22: 174-177 [Abstract] [Full Text]  
  • Shen, H. M., Storb, U. (2004). Activation-induced cytidine deaminase (AID) can target both DNA strands when the DNA is supercoiled. Proc. Natl. Acad. Sci. USA 101: 12997-13002 [Abstract] [Full Text]  
  • Lippert, M. J., Freedman, J. A., Barber, M. A., Jinks-Robertson, S. (2004). Identification of a Distinctive Mutation Spectrum Associated with High Levels of Transcription in Yeast. Mol. Cell. Biol. 24: 4801-4809 [Abstract] [Full Text]  
  • Ochman, H. (2003). Neutral Mutations and Neutral Substitutions in Bacterial Genomes. Mol Biol Evol 20: 2091-2096 [Abstract] [Full Text]  
  • Hudson, R. E., Bergthorsson, U., Ochman, H. (2003). Transcription increases multiple spontaneous point mutations in Salmonella enterica. Nucleic Acids Res 31: 4517-4522 [Abstract] [Full Text]  
  • Sohail, A., Klapacz, J., Samaranayake, M., Ullah, A., Bhagwat, A. S. (2003). Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations. Nucleic Acids Res 31: 2990-2994 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»