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유전체 항상성 연구단
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Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from chromatin

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Title
Ewing sarcoma protein promotes dissociation of poly(ADP-ribose) polymerase 1 from chromatin
Author(s)
Seon-gyeong Lee; Namwoo Kim; Su-min Kim; In Bae Park; Hyejin Kim; Shinseog Kim; Byung-gyu Kim; Jung Me Hwang; In-Joon Baek; Anton Gartner; Jun Hong Park; Kyungjae Myung
Subject
DNA damage response, ; EWS, ; PAR, ; PARP-1, ; PARylation
Publication Date
2020-11
Journal
EMBO REPORTS, v.21, no.11, pp.e48676
Publisher
WILEY
Abstract
© 2020 The Authors. 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
URI
https://pr.ibs.re.kr/handle/8788114/7566
DOI
10.15252/embr.201948676
ISSN
1469-221X
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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