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Journal of Bacteriology, October 2009, p. 6312-6319, Vol. 191, No. 20
0021-9193/09/$08.00+0     doi:10.1128/JB.00613-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Uracil DNA Glycosylase UdgB of Mycobacterium smegmatis Protects the Organism from the Mutagenic Effects of Cytosine and Adenine Deamination{triangledown}

Roger M. Wanner,1,{dagger} Dennis Castor,2,{dagger} Carolin Güthlein,1 Erik C. Böttger,1 Burkhard Springer,1,{ddagger} and Josef Jiricny2*

Institute of Medical Microbiology, University of Zurich, and National Centre for Mycobacteria, Gloriastrasse 30, CH-8006 Zurich, Switzerland,1 Institute of Molecular Cancer Research of the University of Zurich and Department of Biology of the ETH Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland2

Received 11 May 2009/ Accepted 4 August 2009

Spontaneous hydrolytic deamination of DNA bases represents a considerable mutagenic threat to all organisms, particularly those living in extreme habitats. Cytosine is readily deaminated to uracil, which base pairs with adenine during replication, and most organisms encode at least one uracil DNA glycosylase (UDG) that removes this aberrant base from DNA with high efficiency. Adenine deaminates to hypoxanthine approximately 10-fold less efficiently, and its removal from DNA in vivo has to date been reported to be mediated solely by alkyladenine DNA glycosylase. We previously showed that UdgB from Pyrobaculum aerophilum, a hyperthermophilic crenarchaeon, can excise hypoxanthine from oligonucleotide substrates, but as this organism is not amenable to genetic manipulation, we were unable to ascertain that the enzyme also has this role in vivo. In the present study, we show that UdgB from Mycobacterium smegmatis protects this organism against mutagenesis associated with deamination of both cytosine and adenine. Together with Ung-type uracil glycosylase, M. smegmatis UdgB also helps attenuate the cytotoxicity of the antimicrobial agent 5-fluorouracil.

* Corresponding author. Mailing address: Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Phone: 41-44-6353450. Fax: 41-44-6353484. E-mail: jiricny{at}imcr.uzh.ch

{triangledown} Published ahead of print on 14 August 2009.

{dagger} R.M.W. and D.C. contributed equally to this study.

{ddagger} Present address: Institute of Medical Microbiology and Hygiene, Austrian Agency for Health and Food Safety, Beethovenstrasse 6, 8010 Graz, Austria.

Journal of Bacteriology, October 2009, p. 6312-6319, Vol. 191, No. 20
0021-9193/09/$08.00+0     doi:10.1128/JB.00613-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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