PXD020417

PXD020417 is an original dataset announced via ProteomeXchange.

Title	Zinc finger protein ZNF384 is an adaptor of KU to DNA during classical non-homologous end-joining
Description	DNA 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:30:22.858.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Román González-Prieto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-17 08:43:36	ID requested
1	2021-11-15 08:09:02	announced
2	2023-04-11 06:10:44	announced	2023-04-11: Updated project metadata.
⏵ 3	2024-10-22 05:30:23	announced	2024-10-22: Updated project metadata.

10.1038/s41467-021-26691-0;

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]

submitter keyword: Non Homologous End Joining

Double Strand Break Repair;

Alfred CO Vertegaal
contact affiliation	Cell and Chemical Biology Leiden University Medical Center The Netherlands
contact email	vertegaal@lumc.nl
lab head
Román González-Prieto
contact affiliation	Andalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville
contact email	R.Gonzalez_Prieto@lumc.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/11/PXD020417

PRIDE project URI

• PRIDE
  1. PXD020417
     1. Label: PRIDE project
     2. Name: Zinc finger protein ZNF384 is an adaptor of KU to DNA during classical non-homologous end-joining