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PXD020417

PXD020417 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleZinc finger protein ZNF384 is an adaptor of KU to DNA during classical non-homologous end-joining
DescriptionDNA double-strand breaks (DSBs) are among the most deleterious types of DNA damages as they can lead to mutations and chromosomal rearrangements, which underlie cancer development and progression. Non-homologous end-joining (NHEJ) is the dominant pathway for the repair of DSBs in human cells, which involves the DNA binding proteins Ku70/Ku80. Other DNA binding proteins such as Zinc Finger (ZnF) domain-containing proteins have also been implicated in DNA repair. However, their role in NHEJ has remained elusive. Here we show that ZNF384, which is a member of the C2H2 family of ZnF proteins that binds DNA in vitro, is recruited to DSBs in vivo. ZNF384 recruitment requires the PARP/PAR-dependent expansion of damaged chromatin followed by binding of ZNF384 to the exposed DNA via its unique C2H2 motifs. Mass-spectrometry-based experiments revealed that ZNF384 interacts with the Ku70/Ku80 NHEJ complex via its N-terminus. This interaction promotes the assembly of Ku70/Ku80 at DBSs as revealed by fluorescence recovery after photobleaching and fluorescence correlation spectroscopy. By regulating Ku70/80 dynamics, ZNF384 facilitates the assembly of several downstream NHEJ factors (e.g. APLF and XRCC4) and repair by cNHEJ at DSBs. Altogether, our data suggest that ZNF384 acts as a ‘Ku-adaptor’ that binds to DSBs and Ku70/80 to facilitate their binding and the subsequent build-up of a functional cNHEJ repairosome at these lesions, high-lighting a role for ZNF384 in DSB repair and genome maintenance.
HostingRepositoryPRIDE
AnnounceDate2023-04-11
AnnouncementXMLSubmission_2023-04-11_06:10:43.485.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRománGonzález-Prieto
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-07-17 08:43:36ID requested
12021-11-15 08:09:02announced
22023-04-11 06:10:44announced2023-04-11: Updated project metadata.
Publication List
Singh JK, Smith R, Rother MB, de Groot AJL, Wiegant WW, Vreeken K, D'Augustin O, Kim RQ, Qian H, Krawczyk PM, Gonz, á, lez-Prieto R, Vertegaal ACO, Lamers M, Huet S, van Attikum H, Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining. Nat Commun, 12(1):6560(2021) [pubmed]
Keyword List
submitter keyword: Non Homologous End Joining
Double Strand Break Repair;
Contact List
Alfred COVertegaal
contact affiliationCell and Chemical Biology Leiden University Medical Center The Netherlands
contact emailvertegaal@lumc.nl
lab head
RománGonzález-Prieto
contact affiliationAndalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact emailR.Gonzalez_Prieto@lumc.nl
dataset submitter
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Dataset FTP location
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