1. Chromosomes and Gene Expression
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Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae

  1. Nicola Manfrini
  2. Michela Clerici
  3. Maxime Wery
  4. Chiara Vittoria Colombo
  5. Marc Descrimes
  6. Antonin Morillon
  7. Fabrizio d'Adda di Fagagna
  8. Maria Pia Longhese  Is a corresponding author
  1. National Institute of Molecular Genetics Romeo ed Enrica Invernizzi"", Italy
  2. Università di Milano-Bicocca, Italy
  3. Université Pierre et Marie Curie, France
  4. FIRC Institute of Molecular Oncology Foundation, Italy
Research Article
  • Cited 19
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Cite this article as: eLife 2015;4:e08942 doi: 10.7554/eLife.08942

Abstract

Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/ATM and Mec1/ATR. Since the DSB ends undergo nucleolytic degradation (resection) of their 5'-ending strands, we investigated the contribution of resection in this DSB-induced transcriptional inhibition. We discovered that resection-defective mutants fail to stop transcription around a DSB, and the extent of this failure correlates with the severity of the resection defect. Furthermore, Rad9 and generation of γH2A reduce this DSB-induced transcriptional inhibition by counteracting DSB resection. Therefore, the conversion of the DSB ends from double-stranded to single-stranded DNA, which is necessary to initiate DSB repair by homologous recombination, is responsible for loss of transcription around a DSB in S. cerevisiae.

Article and author information

Author details

  1. Nicola Manfrini

    National Institute of Molecular Genetics Romeo ed Enrica Invernizzi"", Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Michela Clerici

    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Maxime Wery

    Institut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Chiara Vittoria Colombo

    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Marc Descrimes

    Institut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Antonin Morillon

    Institut Curie, Dynamics of Genetic Information: Fundamental Basis and Cancer, Université Pierre et Marie Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Fabrizio d'Adda di Fagagna

    IFOM Foundation, FIRC Institute of Molecular Oncology Foundation, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  8. Maria Pia Longhese

    Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy
    For correspondence
    mariapia.longhese@unimib.it
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Jessica K Tyler, University of Texas MD Anderson Cancer Center, United States

Publication history

  1. Received: May 22, 2015
  2. Accepted: July 30, 2015
  3. Accepted Manuscript published: July 31, 2015 (version 1)
  4. Version of Record published: August 19, 2015 (version 2)

Copyright

© 2015, Manfrini et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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