PXD058855-1

PXD058855 is an original dataset announced via ProteomeXchange.

Title	KAT5-mediated acetylation of PC4 facilitates DNA repair by promoting chromatin reorganization
Description	Human positive coactivator 4 (PC4), is a highly abundant non-histone chromatin protein involved in diverse cellular processes, including transcription regulation, genome organization, autophagy, B-cell differentiation, neurogenesis, DNA repair, etc. Most PC4 is phosphorylated in cells, which interacts with core histones and the linker histone H1 to confer the compact heterochromatin state of the genome. Knocking down of PC4 at both cellular and organismal levels leads to significant chromatin decondensation, altered epigenetic landscape, enhanced autophagy, and increased DNA damage susceptibility. Here, we report that besides p300, PC4 also gets acetylated by DNA repair, facilitating lysine acetyltransferase KAT5 (Tip60) at a specific lysine residue (PC4K80) when the cells are subjected to DNA damage. The vulnerability of DNA in PC4 devoid cells was substantially reduced by reintroducing wild-type PC4 to the cells but not the mutant PC4 (PC4K80R), defective in KAT5-mediated acetylation. High-resolution microscopy techniques, including transmission electron microscopy (TEM) and atomic force microscopy (AFM), are employed to visualize chromatin structural changes in response to DNA damage and repair in a Tip60- mediated PC4 acetylation-dependent manner. Presumably, KAT5-mediated acetylation of PC4 at K80 residue facilitates access to the damaged DNA by altering chromatin structures at damage sites, thus promoting DNA repair. This process could be highly significant both in cancer and in aging
HostingRepository	PRIDE
AnnounceDate	2025-10-20
AnnouncementXML	Submission_2025-10-19_17:47:46.642.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD058855
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Tapas Kumar Kundu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-13 07:32:15	ID requested
⏵ 1	2025-10-19 17:47:47	announced

10.6019/PXD058855;

Agrawal A, Sikder S, Singh S, Sharma RK, Pallaprolu N, Mitra K, Mondal S, Mukhopadhyay R, Sarkar J, Peraman R, Ravichandiran V, Kundu TK, KAT5-mediated acetylation of PC4 facilitates DNA repair by promoting chromatin reorganization. Nucleic Acids Res, 53(18):(2025) [pubmed]

10.1093/nar/gkaf974;

submitter keyword: non-histone chromatin protein,Lysine acetyltransferases (KATs), Positive coactivator 4 (PC4), DNA damage, Atomic Force Microscopy (AFM)

Tapas Kumar Kundu
contact affiliation	Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India
contact email	tapas@jncasr.ac.in
lab head
Tapas Kumar Kundu
contact affiliation	Jawaharlal Nehru Centre for Advanced Scientific Research, Rachenahalli lake road, Jakkur, Bangalore-560064
contact email	tapas@jncasr.ac.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058855
     1. Label: PRIDE project
     2. Name: KAT5-mediated acetylation of PC4 facilitates DNA repair by promoting chromatin reorganization