TY - JOUR

T1 - Fused in sarcoma (FUS) in dna repair

T2 - Tango with poly(ADP-ribose) polymerase 1 and compartmentalisation of damaged DNA

AU - Sukhanova, Maria V.

AU - Singatulina, Anastasia S.

AU - Pastré, David

AU - Lavrik, Olga I.

N1 - Funding Information: Funding: This research was funded by the Russian Science Foundation, grant number 20-14-00086 (to M.S.), and by a Russian-state–funded budget project, grant number AAAA-A17-117020210022-4. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/10/1

Y1 - 2020/10/1

N2 - The fused in sarcoma (FUS) protein combines prion-like properties with a multifunctional DNA/RNA-binding domain and has functions spanning the regulation of RNA metabolism, including transcription, pre-mRNA splicing, mRNA transport and translation. In addition to its roles in RNA metabolism, FUS is implicated in the maintenance of DNA integrity. In this review, we examine the participation of FUS in major DNA repair pathways, focusing on DNA repair associated with poly(ADP-ribosyl)ation events and on how the interaction of FUS with poly(ADP-ribose) may orchestrate transient compartmentalisation of DNA strand breaks. Unravelling how prion-like RNA-binding proteins control DNA repair pathways will deepen our understanding of the pathogenesis of some neurological diseases and cancer as well as provide the basis for the development of relevant innovative therapeutic technologies. This knowledge may also extend the range of applications of poly(ADP-ribose) polymerase inhibitors to the treatment of neurodegenerative diseases related to RNA-binding proteins in the cell, e.g., amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

AB - The fused in sarcoma (FUS) protein combines prion-like properties with a multifunctional DNA/RNA-binding domain and has functions spanning the regulation of RNA metabolism, including transcription, pre-mRNA splicing, mRNA transport and translation. In addition to its roles in RNA metabolism, FUS is implicated in the maintenance of DNA integrity. In this review, we examine the participation of FUS in major DNA repair pathways, focusing on DNA repair associated with poly(ADP-ribosyl)ation events and on how the interaction of FUS with poly(ADP-ribose) may orchestrate transient compartmentalisation of DNA strand breaks. Unravelling how prion-like RNA-binding proteins control DNA repair pathways will deepen our understanding of the pathogenesis of some neurological diseases and cancer as well as provide the basis for the development of relevant innovative therapeutic technologies. This knowledge may also extend the range of applications of poly(ADP-ribose) polymerase inhibitors to the treatment of neurodegenerative diseases related to RNA-binding proteins in the cell, e.g., amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

KW - DNA repair

KW - Fused in sarcoma

KW - Poly(ADP-ribose)

KW - Poly(ADP-ribose) polymerase

KW - Protein phase separation

UR - http://www.scopus.com/inward/record.url?scp=85091989708&partnerID=8YFLogxK

U2 - 10.3390/ijms21197020

DO - 10.3390/ijms21197020

M3 - Review article

C2 - 32987654

AN - SCOPUS:85091989708

VL - 21

SP - 1

EP - 18

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 19

M1 - 7020

ER -