CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks

Chromatin structure is dynamically reorganized at multiple levels in response to DNA double-strand breaks (DSBs). Yet, how the different steps of chromatin reorganization are coordinated in space and time to differentially regulate DNA repair pathways is insufficiently understood. Here, we identify...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Nature communications Jg. 11; H. 1; S. 5775 - 19
Hauptverfasser:	Rother, Magdalena B., Pellegrino, Stefania, Smith, Rebecca, Gatti, Marco, Meisenberg, Cornelia, Wiegant, Wouter W., Luijsterburg, Martijn S., Imhof, Ralph, Downs, Jessica A., Vertegaal, Alfred C. O., Huet, Sébastien, Altmeyer, Matthias, van Attikum, Haico
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 13.11.2020 Nature Publishing Group Nature Portfolio
Schlagworte:	13 13/1 13/106 13/109 14/19 14/35 14/63 38/77 38/89 42 631/337/100/102 631/337/1427/2122 631/337/1427/2191 631/337/1427/2566 631/80/458/1275 82/58 82/80 Acetylation Cell Line, Tumor CHARGE syndrome Chromatin - metabolism Chromatin remodeling Damage Deoxyribonucleic acid DNA DNA Breaks, Double-Stranded DNA damage DNA End-Joining Repair DNA helicase DNA Helicases - metabolism DNA Ligase ATP - metabolism DNA repair DNA structure DNA-Binding Proteins - metabolism Double-strand break repair Green Fluorescent Proteins - metabolism Histone Deacetylase 1 - metabolism Homology Humanities and Social Sciences Humans Ku Autoantigen - metabolism Life Sciences LIG4 protein multidisciplinary Non-homologous end joining Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) polymerase Proteins Repair Science Science (multidisciplinary) Tumor Suppressor p53-Binding Protein 1 - metabolism Ubiquitin-Protein Ligases - metabolism Yeast
ISSN:	2041-1723, 2041-1723
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Chromatin structure is dynamically reorganized at multiple levels in response to DNA double-strand breaks (DSBs). Yet, how the different steps of chromatin reorganization are coordinated in space and time to differentially regulate DNA repair pathways is insufficiently understood. Here, we identify the Chromodomain Helicase DNA Binding Protein 7 (CHD7), which is frequently mutated in CHARGE syndrome, as an integral component of the non-homologous end-joining (NHEJ) DSB repair pathway. Upon recruitment via PARP1-triggered chromatin remodeling, CHD7 stimulates further chromatin relaxation around DNA break sites and brings in HDAC1/2 for localized chromatin de-acetylation. This counteracts the CHD7-induced chromatin expansion, thereby ensuring temporally and spatially controlled ‘chromatin breathing’ upon DNA damage, which we demonstrate fosters efficient and accurate DSB repair by controlling Ku and LIG4/XRCC4 activities. Loss of CHD7-HDAC1/2-dependent cNHEJ reinforces 53BP1 assembly at the damaged chromatin and shifts DSB repair to mutagenic NHEJ, revealing a backup function of 53BP1 when cNHEJ fails. Chromatin is dynamically remodeled in response to DNA damage in favour of repair. Here the authors reveal how the chromatin remodeler CHD7 and chromatin binding protein 53BP1 regulate distinct DNA repair pathways.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-19502-5