PXD046037-1

PXD046037 is an original dataset announced via ProteomeXchange.

Title	TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival
Description	DNA repair and autophagy are distinct biological processes vital for cell survival. Although autophagy helps maintain genome stability, there is no evidence of its direct role in the repair of DNA lesions. We discovered that lysosomes process topoisomerase 1 cleavage complexes (TOP1cc) DNA lesions in vertebrates. Selective degradation of TOP1cc by autophagy directs DNA damage repair and cell survival at clinically relevant doses of topoisomerase 1 inhibitors. TOP1cc are exported from the nucleus to lysosomes through a transient alteration of the nuclear envelope and independent of the proteasome. Mechanistically, the autophagy receptor TEX264 acts as a TOP1cc sensor at DNA replication forks, triggering TOP1cc processing by the Q8 p97 ATPase and mediating the delivery of TOP1cc to lysosomes in an MRE11-nuclease- and ATR-kinasedependent manner. We found an evolutionarily conserved role for selective autophagy in DNA repair that enQ2 ables cell survival, protects genome stability, and is clinically relevant for colorectal cancer patients.
HostingRepository	PRIDE
AnnounceDate	2024-09-03
AnnouncementXML	Submission_2024-09-03_09:02:22.343.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	iolanda Vendrell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Ascend

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-10 10:38:25	ID requested
⏵ 1	2024-09-03 09:02:22	announced

10.1016/J.CELL.2024.08.020;

submitter keyword: DNA repair, Topoisomerase 1- cleavage complex, TEX264,Selective autophagy, protein degradation, genome stability

Kristijan Ramadan
contact affiliation	The MRC Weatherall Institute for Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK
contact email	kristijan.ramadan@oncology.ox.ac.uk
lab head
iolanda Vendrell
contact affiliation	Target Discovery Institute, NDMRB
contact email	iolanda.vendrell@ndm.ox.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/2024/09/PXD046037

PRIDE project URI

• PRIDE
  1. PXD046037
     1. Label: PRIDE project
     2. Name: TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival