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The CHD6 chromatin remodeler is an oxidative DNA damage response factor

Author

Listed:
  • Shaun Moore

    (University of Calgary)

  • N. Daniel Berger

    (University of Calgary)

  • Martijn S. Luijsterburg

    (Leiden University Medical Center)

  • Cortt G. Piett

    (School of Public Health)

  • Fintan K. T. Stanley

    (University of Calgary)

  • Christoph U. Schräder

    (University of Calgary)

  • Shujuan Fang

    (University of Calgary)

  • Jennifer A. Chan

    (University of Calgary)

  • David C. Schriemer

    (University of Calgary)

  • Zachary D. Nagel

    (School of Public Health)

  • Haico Attikum

    (Leiden University Medical Center)

  • Aaron A. Goodarzi

    (University of Calgary)

Abstract

Cell survival after oxidative DNA damage requires signaling, repair and transcriptional events often enabled by nucleosome displacement, exchange or removal by chromatin remodeling enzymes. Here, we show that Chromodomain Helicase DNA-binding protein 6 (CHD6), distinct to other CHD enzymes, is stabilized during oxidative stress via reduced degradation. CHD6 relocates rapidly to DNA damage in a manner dependent upon oxidative lesions and a conserved N-terminal poly(ADP-ribose)-dependent recruitment motif, with later retention requiring the double chromodomain and central core. CHD6 ablation increases reactive oxygen species persistence and impairs anti-oxidant transcriptional responses, leading to elevated DNA breakage and poly(ADP-ribose) induction that cannot be rescued by catalytic or double chromodomain mutants. Despite no overt epigenetic or DNA repair abnormalities, CHD6 loss leads to impaired cell survival after chronic oxidative stress, abnormal chromatin relaxation, amplified DNA damage signaling and checkpoint hypersensitivity. We suggest that CHD6 is a key regulator of the oxidative DNA damage response.

Suggested Citation

  • Shaun Moore & N. Daniel Berger & Martijn S. Luijsterburg & Cortt G. Piett & Fintan K. T. Stanley & Christoph U. Schräder & Shujuan Fang & Jennifer A. Chan & David C. Schriemer & Zachary D. Nagel & Hai, 2019. "The CHD6 chromatin remodeler is an oxidative DNA damage response factor," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08111-y
    DOI: 10.1038/s41467-018-08111-y
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    Cited by:

    1. Shweta Godbole & Hannah Voß & Antonia Gocke & Simon Schlumbohm & Yannis Schumann & Bojia Peng & Martin Mynarek & Stefan Rutkowski & Matthias Dottermusch & Mario M. Dorostkar & Andrey Korshunov & Thoma, 2024. "Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level," Nature Communications, Nature, vol. 15(1), pages 1-24, December.

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