PXD005913

PXD005913 is an original dataset announced via ProteomeXchange.

Title	Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break rep
Description	The DNA damage response (DDR) is an extensive signaling network that is robustly mobilized by DNA double-strand breaks (DSBs). The primary transducer of the DSB response is the protein kinase, ataxia-telangiectasia, mutated (ATM). Here, we establish nuclear poly(A)-binding protein 1 (PABPN1) as a novel target of ATM and a crucial player in the DSB response. PABPN1 usually functions in regulation of RNA processing and stability. We establish that PABPN1 is recruited to the DDR as a critical regulator of DSB repair. A portion of PABPN1 relocalizes to DSB sites and is phosphorylated on Ser95 in an ATM-dependent manner. PABPN1 depletion sensitizes cells to DSBinducing agents and prolongs the DSB-induced G2/M cell-cycle arrest, and DSB repair is hampered by PABPN1 depletion or elimination of its phosphorylation site. PABPN1 is required for optimal DSB repair via both nonhomologous end-joining (NHEJ) and homologous recombination repair (HRR), and specifically is essential for efficient DNAend resection, an initial, key step in HRR. Using mass spectrometry analysis, we capture DNA damage-induced interactions of phospho-PABPN1, including well-established DDR players as well as other RNA metabolizing proteins. Our results uncover a novel ATM-dependent axis in the rapidly growing interface between RNA metabolism and the DDR.
HostingRepository	PRIDE
AnnounceDate	2017-11-30
AnnouncementXML	Submission_2018-05-23_06:58:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Geiger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-02-13 01:14:54	ID requested
1	2017-11-30 01:41:11	announced
⏵ 2	2018-05-23 06:58:41	announced	Updated publication reference for PubMed record(s): 29253183.

Gavish-Izakson M, Velpula BB, Elkon R, Prados-Carvajal R, Barnabas GD, Ugalde AP, Agami R, Geiger T, Huertas P, Ziv Y, Shiloh Y, Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break repair. Nucleic Acids Res, 46(2):730-747(2018) [pubmed]

curator keyword: Biological

submitter keyword: PABPN1, mass spectrometry, LC-MS/MS, DNA damage response

Tamar Geiger
contact affiliation	Department of Human Molecular Genetics and Biochemistry Sackler Faculty of Medicine Tel Aviv University Israel
contact email	geiger@tauex.tau.ac.il
lab head
Tamar Geiger
contact affiliation	Tel Aviv University
contact email	geiger@tauex.tau.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005913
     1. Label: PRIDE project
     2. Name: Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break rep