PXD041132

PXD041132 is an original dataset announced via ProteomeXchange.

Title	Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors
Description	Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme Polynucleotide Kinase 3'-Phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:19:51.072.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ignasi Forne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-27 08:24:38	ID requested
1	2024-01-10 00:36:36	announced
⏵ 2	2024-10-22 06:19:51	announced	2024-10-22: Updated project metadata.

10.1093/NAR/GKAD1257;

submitter keyword: DNA repair,Brain cancer, non-homologous end joining, PNKP, DNA damage, pediatric high-grade glioma, replication fork, oncohistone

Sophie Polo
contact affiliation	Epigenetics and Cell Fate Centre CNRS UMR7216 – Université Paris Cité Lamarck B building, 4th floor, room 413 35, rue Hélène Brion 75205 Paris Cedex 13 +33157278981
contact email	sophie.polo@univ-paris-diderot.fr
lab head
Ignasi Forne
contact affiliation	Biomedical Center-LMU
contact email	ignasi.forne@lrz.uni-muenchen.de
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/2024/01/PXD041132

PRIDE project URI

• PRIDE
  1. PXD041132
     1. Label: PRIDE project
     2. Name: Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors