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Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand

Nature Immunology volume 4, pages 452–456 (2003)Cite this article

Abstract

Somatic hypermutation and class switch recombination are DNA modification reactions that alter the genes encoding antibodies in B lymphocytes. Both of these distinct reactions require activation-induced deaminase (AID) and transcription. Here we show that in Escherichia coli, as in eukaryotic cells, the mutation frequency is directly proportional to the transcription of target genes. Transcription enhances mutation of the nontemplate DNA strand, which is exposed as single-stranded DNA during the elongation reaction, but not mutation of the template DNA strand, which is protected by E. coli RNA polymerase. Our results establish a direct link between AID and transcription and suggest that the role of transcription in facilitating mutation is to provide AID with access to single-stranded DNA.

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Figure 1: AIDE.coli induces rapid mutation in E. coli DNA.
Figure 2: Transcription enhances AID-induced mutation.
Figure 3: AID preferentially deaminates cytidine on the nontemplate strand of DNA.

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Acknowledgements

We thank members of the Nussenzweig laboratory, F. Papavasiliou, S. Darst, P. Model and M. Russel for discussions and E. Besmer for help with the manuscript. This work was supported in part by grants from the US National Institutes of Health (to M.C.N.). M.C.N is an Howard Hughes Medical Institute Investigator, P.S. is supported by a grant from the Cancer Research Institute, and A.R.R. is a fellow of the Ministerio de Educacion, Cultura y Deporte.

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  1. Laboratory of Molecular Immunology, Rockefeller University, New York, 10021, NY, USA

    Almudena R. Ramiro, Pete Stavropoulos, Mila Jankovic & Michel C. Nussenzweig

  2. Howard Hughes Medical Institute, Rockefeller University, New York, 10021, NY, USA

    Michel C. Nussenzweig

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Correspondence to Michel C. Nussenzweig.

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Ramiro, A., Stavropoulos, P., Jankovic, M. et al. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand. Nat Immunol 4, 452–456 (2003). https://doi.org/10.1038/ni920

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