PXD020884

PXD020884 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics reveals novel modes of function and inter-relationships among PIKKs in response to genotoxic stress
Description	The DNA damage response (DDR) is a complex signaling network that relies on cascades of protein phosphorylation, which are initiated by three protein kinases of the family of PI3-kinase-related protein kinases (PIKKs): ATM, ATR and DNA-PK. ATM is missing or inactivated in the genome instability syndrome, ataxia-telangiectasia (A-T). The relative shares of these PIKKs in the response to genotoxic stress and the functional relationships among them are central questions in the genome stability field. We conducted a comprehensive phosphoproteomic analysis in human wild-type and A-T cells treated with the double-strand break-inducing chemical, neocarzinostatin, and validated the results with the targeted proteomic technique, selected reaction monitoring. We also matched our results with 34 published screens for DDR factors, creating a valuable resource for identifying strong candidates for novel DDR players. We uncovered fine-tuned dynamics between the PIKKs following genotoxic stress, such as DNA-PK-dependent attenuation of ATM. In A-T cells, partial compensation for ATM absence was provided by ATR and DNA-PK, with distinct roles and kinetics. Our results highlight the intricate relationships between these PIKKs in regulating the DDR.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:15:41.894.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sapir Schlam
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	QTRAP 5500

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-12 22:53:00	ID requested
1	2020-11-24 22:24:38	announced
⏵ 2	2024-10-22 05:15:45	announced	2024-10-22: Updated project metadata.

Schlam-Babayov S, Bensimon A, Harel M, Geiger T, Aebersold R, Ziv Y, Shiloh Y, Phosphoproteomics reveals novel modes of function and inter-relationships among PIKKs in response to genotoxic stress. EMBO J, 40(2):e104400(2021) [pubmed]

10.15252/embj.2020104400;

submitter keyword: ATR,DDR, ATM, DNA-PK, DNA damage

Yosef Shiloh
contact affiliation	Department of Human Molecular Genetics and Biochemistry Tel Aviv University School of Medicine Tel Aviv 69987, Israel
contact email	yossih@tauex.tau.ac.il
lab head
Sapir Schlam
contact affiliation	TAU
contact email	sapir.babayov@gmail.com
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/2020/11/PXD020884

PRIDE project URI

• PRIDE
  1. PXD020884
     1. Label: PRIDE project
     2. Name: Phosphoproteomics reveals novel modes of function and inter-relationships among PIKKs in response to genotoxic stress