Abstract
Translocation and aberrant hypermutation of c-MYC are common in B-cell lymphomas. Activation-induced Cytidine Deaminase (AID) initiates switch recombination and somatic hypermutation in B cells by targeted deamination of transcribed genes. We show that transcription of the immunoglobulin S regions and c-MYC results in formation of similar DNA structures, ‘G-loops’, which contain a cotranscriptional RNA: DNA hybrid on the C-rich strand and single-stranded regions and G4 DNA on the G-rich strand. AID binds specifically to G-loops within transcribed S regions and c-MYC, and G-loops in c-MYC map to the regions associated with translocation breakpoints and aberrant hypermutation in B-cell lymphomas. Aberrant targeting of AID to DNA structures formed upon c-MYC transcription may therefore contribute to the genetic instability of c-MYC in B-cell malignancies.
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Acknowledgements
We thank Molly Weiner for mapping G-loops within transcribed c-MYC, and Anton Krumm (Department of Radiation Oncology, University of Washington Medical Center) for providing the plasmid carrying the human c-MYC gene and Bobbie Schneider and staff for help with the electron microscopy. This research was supported by NIH R01 GM39799 and R01 GM65988 to NM, and R37 GM21422 and R01 ES13192 to MFG.
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Duquette, M., Pham, P., Goodman, M. et al. AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation. Oncogene 24, 5791–5798 (2005). https://doi.org/10.1038/sj.onc.1208746
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DOI: https://doi.org/10.1038/sj.onc.1208746
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