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Physiological functions of programmed DNA breaks in signal-induced transcription

Janusz Puc1, Aneel K Aggarwal2, Michael G Rosenfeld3

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

Nature Reviews. Molecular Cell Biology
|May 25, 2017
PubMed

Insights

Programmed DNA breaks, usually harmful, may actually regulate gene transcription by relieving torsional stress and activating gene regulatory elements. This challenges the traditional view of DNA damage as solely detrimental.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • DNA damage is typically viewed as detrimental to cellular integrity.
  • Signal-dependent transcription is a fundamental cellular process.
  • The role of DNA breaks in gene regulation was previously counterintuitive.

Purpose of the Study:

  • To explore the emerging evidence for programmed DNA breaks in transcription regulation.
  • To discuss the functions of DNA breaks in relieving torsional stress.
  • To investigate the role of DNA breaks in promoter and enhancer activation.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of experimental data on DNA breaks and transcription.
  • Discussion of proposed mechanisms for DNA break involvement.

Main Results:

  • Substantial evidence suggests programmed DNA single- and double-strand breaks can regulate transcription.
  • DNA breaks can alleviate torsional stress within DNA.
  • DNA breaks are implicated in the activation of gene promoters and enhancers.

Conclusions:

  • Programmed DNA breaks play a functional role in specific instances of transcription regulation.
  • This finding recontextualizes DNA damage response pathways in gene expression.
  • DNA breaks contribute to dynamic gene regulation beyond damage repair.

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