PXD047643-1

PXD047643 is an original dataset announced via ProteomeXchange.

Title	Chromosome end protection by RAP1-mediated inhibition of DNA-PK
Description	During classical non-homologous end joining (cNHEJ), DNA-dependent protein kinase (DNA-PK) encapsulates free DNA ends, forming a recruitment platform for downstream end-joining factors including Ligase 4 (LIG4). DNA-PK can also bind telomeres, but does not initiate cNHEJ at this position. How the end joining process is regulated in this context-specific manner is currently unclear. Here we show that the Shelterin components TRF2 and RAP1 form a complex with DNA-PK that directly represses its end joining function at telomeres. Biochemical experiments and cryo-electron microscopy reveal that when bound to TRF2, RAP1 establishes a network of interactions with KU and DNA that prevents DNA-PK from recruiting LIG4. In cells, RAP1 is redundant with the APOLLO nuclease in repressing cNHEJ at chromosome ends, demonstrating that the inhibition of DNA-PK prevents telomere fusions in parallel with overhang-dependent mechanisms. Our experiments show that the end joining function of DNA-PK is specifically and directly repressed at telomeres, describing a molecular mechanism for the maintenance of individual linear chromosomes in mammalian cells.
HostingRepository	PRIDE
AnnounceDate	2025-02-25
AnnouncementXML	Submission_2025-02-25_02:06:48.989.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-08 03:09:38	ID requested
⏵ 1	2025-02-25 02:06:49	announced

Dataset with its publication pending

submitter keyword: RAP1, DNA-PK,RAP1-mediated inhibition, crosslinking

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
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/2025/02/PXD047643

PRIDE project URI

• PRIDE
  1. PXD047643
     1. Label: PRIDE project
     2. Name: Chromosome end protection by RAP1-mediated inhibition of DNA-PK