PXD020884-1

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	2020-11-25
AnnouncementXML	Submission_2020-11-24_22:24:37.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]

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

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

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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