PXD020243

PXD020243 is an original dataset announced via ProteomeXchange.

Title	Proteomics of poly(ADP-ribosyl)ation uncovers a role for HIRA in the chromatin adaptation at ALT telomeres
Description	The synthesis of poly(ADP-ribose) (PAR) reconfigures the local environment and recruits repair complexes to damaged chromatin. The degradation of PAR by PARG is essential for progression and completion of DNA repair. Here, we show that inhibition of PARG disrupts homology-directed repair (HDR) mechanisms that underpin alternative telomere lengthening (ALT). By proteomics, we uncovered a novel role for PARylation in regulating the chromatin assembly factor, HIRA in ALT cancer cells. We show that HIRA is enriched at telomeres during G2 phase and is indispensable for histone H3.3 deposition and telomere DNA synthesis. Depletion of HIRA elicits systemic death of ALT cancer cells was mitigated by re-expression of ATRX protein that is frequently inactivated in ALT tumors. We propose that PARylation enables HIRA to fulfill its essential role in the adaptive response due to ATRX deficiency that pervades ALT cancers.
HostingRepository	PRIDE
AnnounceDate	2020-10-12
AnnouncementXML	Submission_2020-11-17_07:49:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Felipe da Vega Leprevost
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; monohydroxylated residue; acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-07 16:20:49	ID requested
1	2020-10-12 07:28:25	announced
⏵ 2	2020-11-17 07:49:03	announced	2020-11-17: Updated publication reference for PubMed record(s): 33046907.

Hoang SM, Kaminski N, Bhargava R, Barroso-Gonz, á, lez J, Lynskey ML, Garc, í, a-Exp, ó, sito L, Roncaioli JL, Wondisford AR, Wallace CT, Watkins SC, James DI, Waddell ID, Ogilvie D, Smith KM, da Veiga Leprevost F, Mellacharevu D, Nesvizhskii AI, Li J, Ray-Gallet D, Sobol RW, Almouzni G, O'Sullivan RJ, Regulation of ALT-associated homology-directed repair by polyADP-ribosylation. Nat Struct Mol Biol, 27(12):1152-1164(2020) [pubmed]

submitter keyword: Telomere, Chromatin, PARPs, Histone, Cancer

Roderick J. O’Sullivan
contact affiliation	Roderick O’Sullivan Ph.D., Dept. Pharmacology & Chemical Biology, University of Pittsburgh, UPMC Hillman Cancer Center, 5115 Centre Avenue Pittsburgh, PA 15213, USA
contact email	rjo@pitt.edu
lab head
Felipe da Vega Leprevost
contact affiliation	University of Michigan
contact email	felipevl@umich.edu
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/2020/10/PXD020243

PRIDE project URI

• PRIDE
  1. PXD020243
     1. Label: PRIDE project
     2. Name: Proteomics of poly(ADP-ribosyl)ation uncovers a role for HIRA in the chromatin adaptation at ALT telomeres