The CHD6 chromatin remodeler is an oxidative DNA damage response factor.

Autor:	Moore S; Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and/or Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada., Berger ND; Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and/or Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada., Luijsterburg MS; Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Piett CG; Harvard University, School of Public Health, Boston, MA, 02115, USA., Stanley FKT; Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and/or Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada., Schräder CU; Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and/or Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada., Fang S; Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and/or Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada., Chan JA; Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and/or Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada., Schriemer DC; Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and/or Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada., Nagel ZD; Harvard University, School of Public Health, Boston, MA, 02115, USA., van Attikum H; Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands., Goodarzi AA; Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and/or Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada. A.Goodarzi@ucalgary.ca.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2019 Jan 16; Vol. 10 (1), pp. 241. Date of Electronic Publication: 2019 Jan 16.
DOI:	10.1038/s41467-018-08111-y
Abstrakt:	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.
Databáze:	MEDLINE
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