PXD015455

PXD015455 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 is robustly mobilized by double-strand breaks (DSBs) in the DNA. This network relies on extensive cascades of protein phosphorylation and dephosphorylation, which are initiated by three apical protein kinases that belong to the family of PI3-kinase-related protein kinases (PIKKs): ATM, ATR and DNA-PK. Loss of ATM leads to a prototypic 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 DSB-inducing chemical, neocarzinostatin, and validated the results with the targeted proteomic technique selected reaction monitoring (SRM). We uncovered redundant as well as non-redundant roles of the PIKKs following genotoxic stress and obtained evidence of a DNA-PK-dependent attenuation of the ATM response. In A-T cells, partial compensation for ATM absence was provided by ATR and DNA-PK, with distinct roles and kinetics to each of them. Our results shed light on the intricate relationships between the three PIKKs in regulating the DDR.
HostingRepository	PRIDE
AnnounceDate	2020-11-25
AnnouncementXML	Submission_2020-11-24_22:40:51.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; acetylated residue; monohydroxylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-16 01:12:04	ID requested
⏵ 1	2020-11-24 22:40:52	announced

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: Human, DDR, ATM, ATR, DNA-PK, LC-MS/MS

Yosef Shiloh
contact affiliation	The David and Inez Myers Laboratory of Cancer Genetics, 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. PXD015455
     1. Label: PRIDE project
     2. Name: Phosphoproteomics reveals novel modes of function and inter-relationships among PIKKs in response to genotoxic stress