<<< Full experiment listing

PXD040676

PXD040676 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePDHE1α, PARylation, Acetyl-CoA, Acetylation, Histones, DNA damage repair
DescriptionChromatin relaxation is a prerequisite step that allows the DNA repair machinery to access double-strand breaks (DSBs), and local histones around the DNA breaks suffer from prompt acetylation changes. However, an intriguing question remains as to where the large demands of acetyl-CoA is precisely produced promptly. Here, we report that pyruvate dehydrogenase 1α (PDHE1α) catalyzes pyruvate metabolism to provide acetyl-CoA promptly in response to DNA damage. PDHE1α was quickly recruited to chromatin in a PARylation-dependent manner, which further drove acetyl-CoA generation to support local chromatin acetylation around the DSB regions. In turn, this process increased the formation of relaxed chromatin to benefit repair factor loading, thus promoting DSB repair to ultimately maintain genome stability and contribute to the resistance of cancer cells to DNA-damaging treatments in vitro and in vivo. In accordance with this, blocking PARylation-based PDHE1α chromatin recruitment markedly attenuated chromatin relaxation and the DSB repair efficiency, resulting in genome instability and restoration of radiosensitivity. Collectively, these findings reveal an undescribed mechanism that underlies site-directed acetyl-CoA generation involving chromatin-associated PDHE1α and its instrumental function in DNA repair and regulating local chromatin acetylation around DSB sites.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:58:12.428.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJun Zhang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-03-07 20:12:04ID requested
12023-07-26 18:50:11announced
22024-10-22 05:58:12announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: PDHE1α, Acetyl-CoA, DNA damage repair, PARylation, Histones, Acetylation
Contact List
Jun Zhang
contact affiliationjunzh128@szu.edu.cn
contact emailjunzh128@szu.edu.cn
lab head
Jun Zhang
contact affiliationShenzhen University
contact emailjunzh128@szu.edu.cn
dataset submitter
Full Dataset Link List
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/2023/07/PXD040676
PRIDE project URI
Repository Record List
[ + ]