Fused in sarcoma (FUS) in dna repair: Tango with poly(ADP-ribose) polymerase 1 and compartmentalisation of damaged DNA

Maria V. Sukhanova, Anastasia S. Singatulina, David Pastré, Olga I. Lavrik

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number7020
Pages (from-to)1-18
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume21
Issue number19
DOIs
Publication statusPublished - 1 Oct 2020
Externally publishedYes

Keywords

  • DNA repair
  • Fused in sarcoma
  • Poly(ADP-ribose)
  • Poly(ADP-ribose) polymerase
  • Protein phase separation

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