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Phosphorothioation of DNA in bacteria by dnd genes

Nature Chemical Biology volume 3, pages 709–710 (2007)Cite this article

Abstract

Modifications of the canonical structures of DNA and RNA play critical roles in cell physiology, DNA replication, transcription and translation in all organisms. We now report that bacterial dnd gene clusters incorporate sulfur into the DNA backbone as a sequence-selective, stereospecific phosphorothioate modification. To our knowledge, unlike any other DNA or RNA modification systems, DNA phosphorothioation by dnd gene clusters is the first physiological modification described on the DNA backbone.

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Figure 1: Chromatographic analysis of dnd-dependent 35S labeling of genomic DNA.
Figure 2: High-resolution mass spectra of isolated and synthetic dinucleotides containing a phosphorothioate.

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Acknowledgements

We are very grateful to D. Hopwood for his continuous support and encouragement throughout our studies on the DNA S-modification system. We are grateful to L. Cui, B. Chen and J. Son (MIT) and J. Marr (Agilent) for expert assistance with mass spectrometry, to Agilent for access to the XCT Ultra ion-trap mass spectrometer, to T. Murase (Tottori University, Japan) for the generous gift of S. enterica serovar Cerro 87, and to J. Fleckenstein (University of Tennessee Health Sciences Center) for a generous gift of the E. coli strain B7A. Financial support for this work was provided by the Ministry of Science and Technology, the National Science Foundation of China, the Ministry of Education of China, the Shanghai Municipal Council of Science and Technology, the US National Cancer Institute and a Center Grant from the US National Institute of Environmental Health Sciences.

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  1. Lianrong Wang and Shi Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Microbial Metabolism and School of Life Science & Biotechnology, Shanghai Jiaotong University, 1954 Huashan Road, Shanghai, 200030, China

    Lianrong Wang, Shi Chen, Tiegang Xu, Xiufen Zhou, Delin You & Zixin Deng

  2. Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Lianrong Wang, John S Wishnok & Peter C Dedon

  3. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Shi Chen

  4. MIT Center for Environmental Health Sciences, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Koli Taghizadeh, John S Wishnok & Peter C Dedon

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  1. Lianrong Wang
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  2. Shi Chen
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Contributions

L.W. and S.C. contributed equally to this work and were responsible for all of the studies related to the chemical and biochemical characterization of the phosphorothioate bonds. T.X. performed the Dnd phenotype studies depicted in Supplementary Figure 1. T.X., X.Z., D.Y. and Z.D. participated in the development of biochemical methods and the bacterial strains used in the studies. K.T. and J.S.W. developed analytical methods and assisted with performing chromatographic and mass spectrometric studies. P.C.D. was responsible for planning and oversight with the chemical and biochemical characterization of the phosphorothioate bonds. L.W., S.C., Z.D. and P.C.D. wrote the paper. All authors discussed the results and assisted with editing of the manuscript.

Corresponding authors

Correspondence to Zixin Deng or Peter C Dedon.

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Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Table 1, Supplementary Data and Supplementary Methods (PDF 852 kb)

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Wang, L., Chen, S., Xu, T. et al. Phosphorothioation of DNA in bacteria by dnd genes. Nat Chem Biol 3, 709–710 (2007). https://doi.org/10.1038/nchembio.2007.39

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