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Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology

Authors
  • Kargapolova, Yulia1, 2
  • Rehimi, Rizwan1, 1
  • Kayserili, Hülya3
  • Brühl, Joanna4
  • Sofiadis, Konstantinos5
  • Zirkel, Anne1
  • Palikyras, Spiros5
  • Mizi, Athanasia5
  • Li, Yun5
  • Yigit, Gökhan5
  • Hoischen, Alexander6
  • Frank, Stefan1, 1, 7
  • Russ, Nicole1, 1
  • Trautwein, Jonathan4
  • van Bon, Bregje6
  • Gilissen, Christian6
  • Laugsch, Magdalena1, 8
  • Gusmao, Eduardo Gade5
  • Josipovic, Natasa5
  • Altmüller, Janine1
  • And 10 more
  • 1 University of Cologne, Cologne, Germany , Cologne (Germany)
  • 2 University Hospital Cologne, Cologne, Germany , Cologne (Germany)
  • 3 Koç University School of Medicine, Istanbul, Turkey , Istanbul (Turkey)
  • 4 Philipps-University Marburg, Marburg, Germany , Marburg (Germany)
  • 5 University Medical Center Göttingen, Göttingen, Germany , Göttingen (Germany)
  • 6 Radboud University Medical Center, Nijmegen, The Netherlands , Nijmegen (Netherlands)
  • 7 Bayer AG, Wuppertal, Germany , Wuppertal (Germany)
  • 8 University of Heidelberg, Heidelberg, Germany , Heidelberg (Germany)
  • 9 University of Regensburg, Regensburg, Germany , Regensburg (Germany)
  • 10 University Hospital Essen, Essen, Germany , Essen (Germany)
  • 11 Faculté de Médecine, Rennes, France , Rennes (France)
  • 12 University of Cantabria, Santander, Spain , Santander (Spain)
  • 13 University of Göttingen, Göttingen, Germany , Göttingen (Germany)
Type
Published Article
Journal
Nature Communications
Publisher
Springer Nature
Publication Date
May 21, 2021
Volume
12
Issue
1
Identifiers
DOI: 10.1038/s41467-021-23327-1
Source
Springer Nature
License
Green

Abstract

Members of the CHD chromatin remodeler family are implicated in human pathologies, however CHD6 remained poorly studied. Here, the authors show that CHD6 binds to and regulates autophagy and stress response genes across cell types. They identify a clinical mutation that affects its ability to recruit cofactors, leading to impaired autophagy induction and DNA repair.

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