ArticleJournal of experimental neuroscience2019
New Mechanisms of DNA Repair Defects in Fused in Sarcoma-Associated Neurodegeneration: Stage Set for DNA Repair-Based Therapeutics?
Article in Journal of experimental neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.Biomedicines · 2024Review
- Review
- Phase Separation of FUS with Poly(ADP-ribosyl)ated PARP1 Is Controlled by Polyamines, Divalent Metal Cations, and Poly(ADP-ribose) Structure.International journal of molecular sciences · 2024Article
- Article
- Article
- DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders.International journal of molecular sciences · 2022Review
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Protein disulphide isomerase (PDI) is protective against amyotrophic lateral sclerosis (ALS)-related mutant Fused in Sarcoma (FUS) in in vitro models.Scientific reports · 2021Article
- DDX17 is involved in DNA damage repair and modifies FUS toxicity in an RGG-domain dependent manner.Acta neuropathologica · 2021Article
- Genome instability and loss of protein homeostasis: converging paths to neurodegeneration?Open biology · 2021Review
- Multiple ways to a dead end: diverse mechanisms by which ALS mutant genes induce cell death.Cell cycle (Georgetown, Tex.) · 2021Review
- DNA Damage and Repair Deficiency in ALS/FTD-Associated Neurodegeneration: From Molecular Mechanisms to Therapeutic Implication.Frontiers in molecular neuroscience · 2021Review
- The role of hnRNPs in frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica · 2020Review
- The role of DNA damage response in amyotrophic lateral sclerosis.Essays in biochemistry · 2020Review
- Fused in Sarcoma (FUS) in DNA Repair: Tango with Poly(ADP-ribose) Polymerase 1 and Compartmentalisation of Damaged DNA.International journal of molecular sciences · 2020Review
- ALS-derived fibroblasts exhibit reduced proliferation rate, cytoplasmic TDP-43 aggregation and a higher susceptibility to DNA damage.Journal of neurology · 2020Article
- Review
- DNA damage response and repair pathway modulation by non-histone protein methylation: implications in neurodegeneration.Journal of cell communication and signaling · 2020Review
- RTMolecular brain · 2019Article
- DNA double-strand breaks: a potential therapeutic target for neurodegenerative diseases.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2019Review
Corrections and comments
- Comment on
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Genome damage and defective DNA repair are etiologically linked to several neurodegenerative disorders, including fused in sarcoma (FUS)-associated amyotrophic lateral sclerosis (ALS). However, the underlying mechanisms remain enigmatic, which is a roadblock for exploiting genome repair-targeted therapies. Our recent studies identified defects in DNA nick ligation and oxidative damage repair caused by mutations in the RNA/DNA-binding protein FUS in familial ALS patients. In healthy neurons, FUS protects the genome by facilitating PARP1-dependent recruitment of XRCC1/DNA Ligase IIIα (LigIII) to oxidized genome sites and activating LigIII via direct interaction. This is a critical step in the repair of oxidative genome damage, a foremost challenge for postmitotic neurons due to their high oxygen consumption. We discovered that mutant FUS significantly inhibited the recruitment of XRCC1/LigIII to DNA strand breaks, causing defects in DNA ligation during the repair of oxidative DNA damage, which contributed to neurodegeneration. While the FUS loss of function was responsible for the repair defects, increased oxidative genome damage due to mutant FUS aggregation could exacerbate the phenomenon. We highlight how these new molecular insights into previously undescribed DNA repair defect linked to FUS-associated neurodegeneration could provide an important opportunity for exploring DNA repair-based therapeutic avenues.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.