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Physiological functions of programmed DNA breaks in signal-induced transcription

Nature Reviews Molecular Cell Biology volume 18, pages 471–476 (2017)Cite this article

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Abstract

The idea that signal-dependent transcription might involve the generation of transient DNA nicks or even breaks in the regulatory regions of genes, accompanied by activation of DNA damage repair pathways, would seem to be counterintuitive, as DNA damage is usually considered harmful to cellular integrity. However, recent studies have generated a substantial body of evidence that now argues that programmed DNA single- or double-strand breaks can, at least in specific cases, have a role in transcription regulation. Here, we discuss the emerging functions of DNA breaks in the relief of DNA torsional stress and in promoter and enhancer activation.

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Figure 1: Transcription regulation by DNA topoisomerases 1 and 2.
Figure 2: 'Programmed' DNA damage.

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Acknowledgements

The authors apologize to all researchers whose important contributions could not be acknowledged owing to space limitations. The authors thank members of the Rosenfeld laboratory for their comments on the work, and are particularly grateful to P. Cortes and E.P. Geiduschek for discussions. This work was supported by DK 018477, DK 039949, and CA17390. M.G.R. is an Investigator with the Howard Hughes Medical Institute (HHMI).

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Authors and Affiliations

  1. Department of Medicine, Janusz Puc is currently at the EMD Serono Research and Development Institute, Billerica, Massachusetts 01821, USA; he was previously at the Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, California 92093-0648, USA.,

    Janusz Puc

  2. Department of Medicine, he was previously at the Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, California 92093-0648, USA.,

    Janusz Puc

  3. Aneel K. Aggarwal is at the Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.,

    Aneel K. Aggarwal

  4. Department of Medicine, Michael G. Rosenfeld is at the Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, California 92093-0648, USA.,

    Michael G. Rosenfeld

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Correspondence to Michael G. Rosenfeld.

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Puc, J., Aggarwal, A. & Rosenfeld, M. Physiological functions of programmed DNA breaks in signal-induced transcription. Nat Rev Mol Cell Biol 18, 471–476 (2017). https://doi.org/10.1038/nrm.2017.43

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