PXD016145

PXD016145 is an original dataset announced via ProteomeXchange.

Title	Ewing sarcoma protein-mediated regulation of poly(ADP-ribose) polymerase 1 dissociation
Description	Poly(ADP-ribose) polymerase 1 (PARP1) critically facilitates DNA damage response (DDR) that suppresses genomic instability. However, the physiological function of PARP1 in regulating genomic integrity is unclear. We investigated the Ewing’s sarcoma breakpoint region 1 (EWS) and found that it regulated the physiological function of PARP1. EWS was indispensable to dissociation of PARP1 from damaged DNA, promoting DDR and regulating DDR protein expression. Abnormal PARP1 accumulation due to EWS expression silencing, induced hyper-PARylation, which exhausted cellular NAD+ levels and caused cell death in in vitro and in vivo. Positively charged EWS arginine-glycine-glycine (Arg-Gly-Gly, RGG) domains directly interact with poly ADP-ribose (PAR) chains produced by PARP1 and are essential to dissociate PARP1 from damaged DNA. Consistently, Ewing’s sarcoma cells with defective EWS function accumulated PARP1 on chromatin and tissues from Ewing’s sarcoma patients, exhibiting high PARylation levels. Taken together, loss of EWS causes defects in PARP1 dissociation and results in genomic instability.
HostingRepository	PRIDE
AnnounceDate	2020-11-03
AnnouncementXML	Submission_2020-11-03_03:37:40.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Byung-gyu kim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	6x(13)C labeled residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-05 05:55:31	ID requested
⏵ 1	2020-11-03 03:37:40	announced

Lee SG, Kim N, Kim SM, Park IB, Kim H, Kim S, Kim BG, Hwang JM, Baek IJ, Gartner A, Park JH, Myung K, Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from chromatin. EMBO Rep, 21(11):e48676(2020) [pubmed]

submitter keyword: EWS, PARP-1, DNA damage response (DDR), PARylation, PAR

Kyungjae Myung
contact affiliation	Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea
contact email	kmyung@ibs.re.kr
lab head
Byung-gyu kim
contact affiliation	Center for genomic integrity (CGI), Institute of basic science (IBS), UNIST, Ulsan, 44919, Republic of Korea
contact email	goldenlion@ibs.re.kr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016145
     1. Label: PRIDE project
     2. Name: Ewing sarcoma protein-mediated regulation of poly(ADP-ribose) polymerase 1 dissociation