PMID- 33006225
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20220531
IS  - 1469-3178 (Electronic)
IS  - 1469-221X (Print)
IS  - 1469-221X (Linking)
VI  - 21
IP  - 11
DP  - 2020 Nov 5
TI  - Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from 
      chromatin.
PG  - e48676
LID - 10.15252/embr.201948676 [doi]
LID - e48676
AB  - Poly(ADP-ribose) polymerase 1 (PARP1) facilitates DNA damage response (DDR). 
      While the Ewing's sarcoma breakpoint region 1 (EWS) protein fused to FLI1 
      triggers sarcoma formation, the physiological function of EWS is largely unknown. 
      Here, we investigate the physiological role of EWS in regulating PARP1. We show 
      that EWS is required for PARP1 dissociation from damaged DNA. Abnormal PARP1 
      accumulation caused by EWS inactivation leads to excessive Poly(ADP-Ribosy)lation 
      (PARylation) and triggers cell death in both in vitro and in vivo models. 
      Consistent with previous work, the arginine-glycine-glycine (RGG) domain of EWS 
      is essential for PAR chain interaction and PARP1 dissociation from damaged DNA. 
      Ews and Parp1 double mutant mice do not show improved survival, but 
      supplementation with nicotinamide mononucleotides extends Ews-mutant pups' 
      survival, which might be due to compensatory activation of other PARP proteins. 
      Consistently, PARP1 accumulates on chromatin in Ewing's sarcoma cells expressing 
      an EWS fusion protein that cannot interact with PARP1, and tissues derived from 
      Ewing's sarcoma patients show increased PARylation. Taken together, our data 
      reveal that EWS is important for removing PARP1 from damaged chromatin.
CI  - (c) 2020 The Authors.
FAU - Lee, Seon-Gyeong
AU  - Lee SG
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
AD  - Department of Biological Sciences, School of Life Sciences, Ulsan National 
      Institute of Science and Technology, Ulsan, Korea.
FAU - Kim, Namwoo
AU  - Kim N
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
AD  - Department of Biological Sciences, School of Life Sciences, Ulsan National 
      Institute of Science and Technology, Ulsan, Korea.
FAU - Kim, Su-Min
AU  - Kim SM
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
AD  - Department of Biological Sciences, School of Life Sciences, Ulsan National 
      Institute of Science and Technology, Ulsan, Korea.
FAU - Park, In Bae
AU  - Park IB
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
FAU - Kim, Hyejin
AU  - Kim H
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
FAU - Kim, Shinseog
AU  - Kim S
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
FAU - Kim, Byung-Gyu
AU  - Kim BG
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
FAU - Hwang, Jung Me
AU  - Hwang JM
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
FAU - Baek, In-Joon
AU  - Baek IJ
AUID- ORCID: 0000-0001-7286-3831
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
FAU - Gartner, Anton
AU  - Gartner A
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
AD  - Department of Biological Sciences, School of Life Sciences, Ulsan National 
      Institute of Science and Technology, Ulsan, Korea.
FAU - Park, Jun Hong
AU  - Park JH
AUID- ORCID: 0000-0001-8905-4125
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
AD  - Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 
      Naju, Korea.
FAU - Myung, Kyungjae
AU  - Myung K
AUID- ORCID: 0000-0001-7975-6190
AD  - Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea.
AD  - Department of Biological Sciences, School of Life Sciences, Ulsan National 
      Institute of Science and Technology, Ulsan, Korea.
LA  - eng
GR  - IBS-R022-D1/Institute for Basic Science (IBS)/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201001
PL  - England
TA  - EMBO Rep
JT  - EMBO reports
JID - 100963049
RN  - 0 (Chromatin)
RN  - 0 (RNA-Binding Protein EWS)
RN  - EC 2.4.2.30 (Parp1 protein, mouse)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
SB  - IM
MH  - Animals
MH  - Chromatin/genetics
MH  - DNA Damage
MH  - Dissociative Disorders
MH  - Humans
MH  - Mice
MH  - Poly (ADP-Ribose) Polymerase-1
MH  - RNA-Binding Protein EWS/genetics/metabolism
MH  - *Sarcoma, Ewing/genetics
PMC - PMC7645264
OTO - NOTNLM
OT  - EWS
OT  - PAR
OT  - DNA damage response
OT  - PARP-1
OT  - PARylation
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/10/03 06:00
MHDA- 2021/04/28 06:00
PMCR- 2021/11/05
CRDT- 2020/10/02 05:50
PHST- 2019/06/16 00:00 [received]
PHST- 2020/08/30 00:00 [revised]
PHST- 2020/09/15 00:00 [accepted]
PHST- 2020/10/03 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/10/02 05:50 [entrez]
PHST- 2021/11/05 00:00 [pmc-release]
AID - EMBR201948676 [pii]
AID - 10.15252/embr.201948676 [doi]
PST - ppublish
SO  - EMBO Rep. 2020 Nov 5;21(11):e48676. doi: 10.15252/embr.201948676. Epub 2020 Oct 
      1.