Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
FUS RRM regulates poly(ADP-ribose) levels after transcriptional arrest and PARP-1 activation on DNA damage. / Mamontova, Evgeniya M; Clément, Marie-Jeanne; Sukhanova, Maria V и др.
в: Cell Reports, Том 42, № 10, 113199, 31.10.2023.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - FUS RRM regulates poly(ADP-ribose) levels after transcriptional arrest and PARP-1 activation on DNA damage
AU - Mamontova, Evgeniya M
AU - Clément, Marie-Jeanne
AU - Sukhanova, Maria V
AU - Joshi, Vandana
AU - Bouhss, Ahmed
AU - Rengifo-Gonzalez, Juan Carlos
AU - Desforges, Bénédicte
AU - Hamon, Loic
AU - Lavrik, Olga I
AU - Pastré, David
N1 - This work was supported in part by the Re´gion Ile-de-France (SESAME grant no. 15013102) and Genopole (SATURNE grant 2020). This study was supported by the Russian Science Foundation (RSF 22-14-00112 to O.I.L. and RSF 20-14-00086 to M.V.S.) and the International doctoral action (ADI2019) program of Paris-Saclay Universite´ (PhD grant to E.M.M.). The graphical abstract was created with BioRender.com Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2023/10/31
Y1 - 2023/10/31
N2 - PARP-1 activation at DNA damage sites leads to the synthesis of long poly(ADP-ribose) (PAR) chains, which serve as a signal for DNA repair. Here we show that FUS, an RNA-binding protein, is specifically directed to PAR through its RNA recognition motif (RRM) to increase PAR synthesis by PARP-1 in HeLa cells after genotoxic stress. Using a structural approach, we also identify specific residues located in the FUS RRM, which can be PARylated by PARP-1 to control the level of PAR synthesis. Based on the results of this work, we propose a model in which, following a transcriptional arrest that releases FUS from nascent mRNA, FUS can be recruited by PARP-1 activated by DNA damage to stimulate PAR synthesis. We anticipate that this model offers new perspectives to understand the role of FET proteins in cancers and in certain neurodegenerative diseases such as amyotrophic lateral sclerosis.
AB - PARP-1 activation at DNA damage sites leads to the synthesis of long poly(ADP-ribose) (PAR) chains, which serve as a signal for DNA repair. Here we show that FUS, an RNA-binding protein, is specifically directed to PAR through its RNA recognition motif (RRM) to increase PAR synthesis by PARP-1 in HeLa cells after genotoxic stress. Using a structural approach, we also identify specific residues located in the FUS RRM, which can be PARylated by PARP-1 to control the level of PAR synthesis. Based on the results of this work, we propose a model in which, following a transcriptional arrest that releases FUS from nascent mRNA, FUS can be recruited by PARP-1 activated by DNA damage to stimulate PAR synthesis. We anticipate that this model offers new perspectives to understand the role of FET proteins in cancers and in certain neurodegenerative diseases such as amyotrophic lateral sclerosis.
KW - ALS
KW - CP: Molecular biology
KW - DNA damage response
KW - DNA repair
KW - FUS/TLS
KW - RNA
KW - RNA-binding proteins
KW - cancer
KW - liquid-liquid phase separation
KW - poly(ADP-ribose)
KW - poly(ADP-ribose) polymerase 1
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85173685628&origin=inward&txGid=0a5d8648094c65f26f9626f53dbfc220
UR - https://www.mendeley.com/catalogue/223c3ca3-8c96-323e-967d-439fa79bdea4/
U2 - 10.1016/j.celrep.2023.113199
DO - 10.1016/j.celrep.2023.113199
M3 - Article
C2 - 37804508
VL - 42
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 10
M1 - 113199
ER -
ID: 55811135