PXD040676-1

PXD040676 is an original dataset announced via ProteomeXchange.

Title	PDHE1α, PARylation, Acetyl-CoA, Acetylation, Histones, DNA damage repair
Description	Chromatin 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.
HostingRepository	PRIDE
AnnounceDate	2023-07-27
AnnouncementXML	Submission_2023-07-26_18:50:10.889.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JunZhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-07 20:12:04	ID requested
⏵ 1	2023-07-26 18:50:11	announced
2	2024-10-22 05:58:12	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: PDHE1α, Acetyl-CoA, DNA damage repair, PARylation, Histones, Acetylation

JunZhang
contact affiliation	junzh128@szu.edu.cn
contact email	junzh128@szu.edu.cn
lab head
JunZhang
contact affiliation	Shenzhen University
contact email	junzh128@szu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040676
     1. Label: PRIDE project
     2. Name: PDHE1α, PARylation, Acetyl-CoA, Acetylation, Histones, DNA damage repair