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PXD046037-1

PXD046037 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival
DescriptionDNA 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.
HostingRepositoryPRIDE
AnnounceDate2024-09-03
AnnouncementXMLSubmission_2024-09-03_09:02:22.343.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitteriolanda Vendrell
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Ascend
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-10-10 10:38:25ID requested
12024-09-03 09:02:22announced
Publication List
10.1016/J.CELL.2024.08.020;
Keyword List
submitter keyword: DNA repair, Topoisomerase 1- cleavage complex, TEX264,Selective autophagy, protein degradation, genome stability
Contact List
Kristijan Ramadan
contact affiliationThe MRC Weatherall Institute for Molecular Medicine, Department of Oncology, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK
contact emailkristijan.ramadan@oncology.ox.ac.uk
lab head
iolanda Vendrell
contact affiliationTarget Discovery Institute, NDMRB
contact emailiolanda.vendrell@ndm.ox.ac.uk
dataset submitter
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Dataset FTP location
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