PXD061039-1

PXD061039 is an original dataset announced via ProteomeXchange.

Title	Ku80 lysine crotonylation conversion to SUMOylation facilitates DNA non-homologous end joining and cellular resistance to radiation
Description	A DNA double-strand break (DSB) is the most serious DNA damage and is also the principal molecular basis of radiotherapy. Upon DNA damage, the Ku80 is recruited and forms a critical DNA-PK complex at the DSB sites with Ku70 and the catalytic subunit (DNA-PKcs) to initiate DNA repair. How DNA-PK is assembled and activated is not fully understood. Based on the identification of radiation-reduced Ku80 K568 crotonylation through quantitative global lysine crotonylome analysis, we reveal that Ku80 K568 is crotonylated by p300-CBP-associated factor (PCAF). Upon DNA damage, the K568cr is decrotonylated by HDAC8. Decrotonylation of K568cr empties this site for the subsequent SUMOylation of Ku80 by CBX4.The conversion of Ku80 from K568 crotonylation to SUMOylation facilitates the assembly of DNA-PK complex and autophosphorylation of DNA-PKcs S2056, consequently activating the DSB repair. Moreover, mutation disrupting the post-translational modification (PTM) of Ku80 K568 site sensitizes cancer cells to radiotherapy in tumor-bearing nude mice models. Our findings provide fresh insights into the regulation of DNA-PK complex assembly and DSB repair. The conversion model between two different forms of post-translational modifications (PTMs) expands the atlas of therapeutic targets.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_07:38:00.169.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	hongling zhao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	crotonylated L-lysine
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-21 01:47:39	ID requested
⏵ 1	2025-05-07 07:38:01	announced

Zhao H, Gao S, Han Y, Xie D, Xuan L, Huang X, Luo J, Ran Q, Li G, Guo H, Hu W, Jia J, Liu X, Liu Y, Tan J, Bai C, Gu Y, Ma T, Li Z, Guan H, Huang R, Zhou PK, Conversion of Ku80 K568 crotonylation to SUMOylation facilitates DNA non-homologous end joining and cancer radioresistance. Signal Transduct Target Ther, 10(1):127(2025) [pubmed]

10.1038/s41392-025-02210-1;

submitter keyword: DNA double-strand break repair

Ku80

crotonylation

SUMOylation

DNA-PK holoenzyme assembly

radioresistance

Pingkun Zhou
contact affiliation	Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, China
contact email	zhoupk@bmi.ac.cn
lab head
hongling zhao
contact affiliation	Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, China
contact email	15735179923@163.com
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/2025/05/PXD061039

PRIDE project URI

• PRIDE
  1. PXD061039
     1. Label: PRIDE project
     2. Name: Ku80 lysine crotonylation conversion to SUMOylation facilitates DNA non-homologous end joining and cellular resistance to radiation