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dc.contributor.authorRother, MB
dc.contributor.authorPellegrino, S
dc.contributor.authorSmith, R
dc.contributor.authorGatti, M
dc.contributor.authorMeisenberg, C
dc.contributor.authorWiegant, WW
dc.contributor.authorLuijsterburg, MS
dc.contributor.authorImhof, R
dc.contributor.authorDowns, JA
dc.contributor.authorVertegaal, ACO
dc.contributor.authorHuet, S
dc.contributor.authorAltmeyer, M
dc.contributor.authorvan Attikum, H
dc.date.accessioned2021-01-28T15:38:09Z
dc.date.available2021-01-28T15:38:09Z
dc.date.issued2020-11-13
dc.identifier.citationNature communications, 2020, 11 (1), pp. 5775 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4330
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-020-19502-5
dc.description.abstractChromatin 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.
dc.formatElectronic
dc.format.extent5775 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectChromatin
dc.subjectHumans
dc.subjectDNA Helicases
dc.subjectUbiquitin-Protein Ligases
dc.subjectDNA-Binding Proteins
dc.subjectGreen Fluorescent Proteins
dc.subjectDNA Breaks, Double-Stranded
dc.subjectHistone Deacetylase 1
dc.subjectDNA End-Joining Repair
dc.subjectKu Autoantigen
dc.subjectDNA Ligase ATP
dc.subjectPoly (ADP-Ribose) Polymerase-1
dc.subjectTumor Suppressor p53-Binding Protein 1
dc.titleCHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks.
dc.typeJournal Article
dcterms.dateAccepted2020-10-15
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-020-19502-5
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-11-13
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Epigenetics and Genome Stability
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Epigenetics and Genome Stability
pubs.publication-statusPublished
pubs.volume11
pubs.embargo.termsNot known
icr.researchteamEpigenetics and Genome Stability
icr.researchteamEpigenetics and Genome Stabilityen_US
dc.contributor.icrauthorDowns, Jessicaen


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