The DNA damage response (DDR) is induced by the C9orf72 repeat expansion in amyotrophic lateral sclerosis

No abstract is available for this paper.

• Publication year

  2017

• Venue

  Human Molecular Genetics

• Publication date

  2017-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1093/hmg/ddx170PMID 28481984
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects.

  2021cited by this paper
• The Role of Dipeptide Repeats in C9ORF72-Related ALS-FTD

  2017cited by this paper
• Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage

  2016cited by this paper
• NEK1 mutations in familial amyotrophic lateral sclerosis.

  2016cited by this paper
• Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons.

  2016cited by this paper
• There has been an awakening: Emerging mechanisms of C9orf72 mutations in FTD/ALS.

  2016cited by this paper
• Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair.

  2016cited by this paper
• Accumulation of dipeptide repeat proteins predates that of TDP‐43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene

  2015cited by this paper
• Nucleolar stress and impaired stress granule formation contribute to C9orf72 RAN translation-induced cytotoxicity.

  2015cited by this paper
• The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair.

  2015cited by this paper
• The C9orf72 repeat expansion itself is methylated in ALS and FTLD patients

  2015cited by this paper
• Dipeptide repeat protein inclusions are rare in the spinal cord and almost absent from motor neurons in C9ORF72 mutant amyotrophic lateral sclerosis and are unlikely to cause their degeneration

  2015cited by this paper
• ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects.

  2014cited by this paper
• Characterization of DNA hypermethylation in the cerebellum of c9FTD/ALS patients.

  2014cited by this paper
• Emerging Roles of the Nucleolus in Regulating the DNA Damage Response: The Noncanonical DNA Repair Enzyme APE1/Ref-1 as a Paradigmatical Example

  2014cited by this paper
• Poly-dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells

  2014cited by this paper
• C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins

  2014cited by this paper
• Functional regulation of the apurinic/apyrimidinic endonuclease 1 by nucleophosmin: impact on tumor biology

  2014cited by this paper
• Partial inhibition of Cdk1 in G2 phase overrides the SAC and decouples mitotic events

  2014cited by this paper
• Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion

  2014cited by this paper
• Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions

  2014cited by this paper
• Base excision repair of oxidative DNA damage coupled with removal of a CAG repeat hairpin attenuates trinucleotide repeat expansion

  2014cited by this paper
• Nucleotide Structural Polymorphisms Formed by GGGGCC Repeats Cause C9orf72 Abortive Transcription and Nucleolar Stress

  2014cited by this paper
• C9orf72 Nucleotide Repeat Structures Initiate Molecular Cascades of Disease

  2014cited by this paper
• Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins

  2014cited by this paper
• Genome-Wide Profiling of Yeast DNA:RNA Hybrid Prone Sites with DRIP-Chip

  2014cited by this paper
• Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS.

  2013cited by this paper
• The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS

  2013cited by this paper
• Hypermethylation of the CpG island near the G4C2 repeat in ALS with a C9orf72 expansion.

  2013cited by this paper
• Reduced C9orf72 gene expression in c9FTD/ALS is caused by histone trimethylation, an epigenetic event detectable in blood

  2013cited by this paper
• RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia

  2013cited by this paper
• Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons

  2013cited by this paper
• RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention.

  2013cited by this paper
• C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci

  2013cited by this paper
• Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations

  2013cited by this paper
• Dipeptide repeat proteins are present in the p62 positive inclusions in patients with frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72

  2013cited by this paper
• TMPyP4 Porphyrin Distorts RNA G-quadruplex Structures of the Disease-associated r(GGGGCC)n Repeat of the C9orf72 Gene and Blocks Interaction of RNA-binding Proteins*

  2013cited by this paper
• R loops: from transcription byproducts to threats to genome stability.

  2012cited by this paper
• Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research.

  2012cited by this paper
• C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms RNA G-quadruplexes

  2012cited by this paper
• Histone H2AX phosphorylation: a marker for DNA damage.

  2012cited by this paper
• Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS.

  2011cited by this paper
• A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.

  2011cited by this paper
• Nucleolar Disruption in Dopaminergic Neurons Leads to Oxidative Damage and Parkinsonism through Repression of Mammalian Target of Rapamycin Signaling

  2011cited by this paper
• Quantitative Proteomics and Dynamic Imaging of the Nucleolus Reveal Distinct Responses to UV and Ionizing Radiation*

  2011cited by this paper
• Nek1 kinase functions in DNA damage response and checkpoint control through a pathway independent of ATM and ATR

  2011cited by this paper
• Mice with DNA repair gene Ercc1 deficiency in a neural crest lineage are a model for late-onset Hirschsprung disease.

  2010cited by this paper
• Increased SOD1 association with chromatin, DNA damage, p53 activation, and apoptosis in a cellular model of SOD1-linked ALS.

  2010cited by this paper
• Recruitment of phosphorylated NPM1 to sites of DNA damage through RNF8-dependent ubiquitin conjugates.

  2010cited by this paper
• NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling

  2010cited by this paper
• Ape1/Ref-1 Induces Glial Cell-Derived Neurotropic Factor (GDNF) Responsiveness by Upregulating GDNF Receptor α1 Expression

  2009cited by this paper
• APE1/Ref-1 Interacts with NPM1 within Nucleoli and Plays a Role in the rRNA Quality Control Process

  2009cited by this paper
• Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases

  2008cited by this paper
• γ-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin

  2008cited by this paper
• The nucleolar SUMO‐specific protease SENP3 reverses SUMO modification of nucleophosmin and is required for rRNA processing

  2008cited by this paper
• Lack of changes in the PI3K/AKT survival pathway in the spinal cord motor neurons of a mouse model of familial amyotrophic lateral sclerosis.

  2007cited by this paper
• Association of the hOGG1 Ser326Cys polymorphism with sporadic amyotrophic lateral sclerosis.

  2007cited by this paper
• Activation and regulation of ATM kinase activity in response to DNA double-strand breaks

  2007cited by this paper
• Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin‐1

  2006cited by this paper
• Poly(ADP-ribose) polymerase-1 activation during DNA damage and repair.

  2006cited by this paper
• Nucleophosmin and cancer

  2006cited by this paper
• Slipped (CTG)•(CAG) repeats can be correctly repaired, escape repair or undergo error-prone repair

  2005cited by this paper
• APE1 overexpression in XRCC1-deficient cells complements the defective repair of oxidative single strand breaks but increases genomic instability

  2005cited by this paper
• 53BP1, an activator of ATM in response to DNA damage.

  2004cited by this paper
• Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination.

  2003cited by this paper
• The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins

  2002cited by this paper
• DNA base-excision repair enzyme apurinic/apyrimidinic endonuclease/redox factor-1 is increased and competent in the brain and spinal cord of individuals with amyotrophic lateral sclerosis

  2002cited by this paper
• Role of phosphatidylinositol 3-kinase-Akt pathway in nucleophosmin/anaplastic lymphoma kinase-mediated lymphomagenesis.

  2001cited by this paper
• Neuronal cell death in nervous system development, disease, and injury (Review).

  2001cited by this paper
• A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage.

  2000cited by this paper
• Mutant AP endonuclease in patients with amyotrophic lateral sclerosis

  1998cited by this paper
• APE/Ref‐1 responses to oxidative stress in aged rats

  1998cited by this paper
• DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139*

  1998cited by this paper
• Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis

  1997cited by this paper

• R-loops as dynamic non-coding genome variations: Mechanisms, disease relevance, and therapeutic opportunities

  2026cites this paper
• Aberrant CDK4/6-driven cell-cycle reentry drives neuronal loss and defines a therapeutic target in C9orf72 ALS/FTD

  2026cites this paper
• Histone Post-Translational Modifications and DNA Double-Strand Break Repair in Neurodegenerative Diseases: An Epigenetic Perspective

  2025cites this paper
• Targeting STAU1 prevents p53 apoptotic signaling in neurodegeneration

  2025cites this paper
• Glial cell-intrinsic and non-cell autonomous toxicity in a Drosophila C9orf72 neurodegeneration model

  2025cites this paper
• C9orf72 Dipeptide Repeat Proteinopathy Is Linked to Increased Histone H3 Phosphorylation on Serine 10

  2025cites this paper
• Roles and therapeutic potential of PARP-1 in neurodegenerative diseases.

  2025cites this paper
• AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice

  2025cites this paper
• Targeting the serotonergic system in the treatment of neurodegenerative diseases—emerging therapies and unmet challenges

  2025cites this paper
• Pathological forms of TDP-43 in amyotrophic lateral sclerosis (ALS) promote aberrant telomere elongation.

  2025cites this paper
• The Molecular Intersection of NEK1, C21ORF2, Cyclin F, and VCP in ALS Pathogenesis

  2025influential citation
• A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies

  2025cites this paper
• Mechanisms underlining R-loop biology and implications for human disease

  2025cites this paper
• The phenotyping dilemma in VRK1-related motor neuron disease: a Turkish family with young-onset amyotrophic lateral sclerosis caused by a novel mutation

  2025cites this paper
• C9orf72-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review

  2025cites this paper
• Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia

  2024cites this paper
• Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair

  2024cites this paper
• RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD

  2024cites this paper
• Intersection of the fragile X-related disorders and the DNA damage response.

  2024cites this paper
• C9orf72 repeat expansion creates the unstable folate-sensitive fragile site FRA9A

  2024cites this paper
• The role of interferon signaling in neurodegeneration and neuropsychiatric disorders

  2024cites this paper
• Update on R-loops in genomic integrity: Formation, functions, and implications for human diseases

  2024cites this paper
• Deep learning-enhanced R-loop prediction provides mechanistic implications for repeat expansion diseases

  2024cites this paper
• Spatially heterogeneous dynamics of droplets formed by arginine-rich dipeptides and poly-A RNA during liquid-liquid phase separation

  2024cites this paper
• Chronological and Biological Aging in Amyotrophic Lateral Sclerosis and the Potential of Senolytic Therapies

  2024cites this paper
• Post-mortem evidence for a reciprocal relationship between genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies

  2024cites this paper
• R-loop and diseases: the cell cycle matters

  2024cites this paper
• Somatic and intergenerational G4C2 hexanucleotide repeat instability in a human C9orf72 knock-in mouse model

  2024cites this paper
• Physiological and pathological effects of phase separation in the central nervous system

  2024cites this paper
• Molecular hallmarks of ageing in amyotrophic lateral sclerosis

  2024cites this paper
• The Long Non-Coding RNA NR3C2-8:1 Promotes p53-Mediated Apoptosis through the miR-129-5p/USP10 Axis in Amyotrophic Lateral Sclerosis

  2024cites this paper
• DNA methylome, R-loop and clinical exome profiling of patients with sporadic amyotrophic lateral sclerosis

  2024cites this paper
• Metformin ameliorates mitochondrial damage induced by C9orf72 poly(GR) via upregulating AKT phosphorylation

  2024cites this paper
• SYF2 suppression mitigates neurodegeneration in models of diverse forms of ALS.

  2023cites this paper
• Chemotherapy-induced neuronal DNA damage: an intriguing toolbox to elucidate DNA repair mechanisms in the brain

  2023cites this paper
• Loss of TDP-43 function contributes to genomic instability in amyotrophic lateral sclerosis

  2023cites this paper
• Poly (ADP-Ribose) Polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities.

  2023cites this paper
• Disrupted phase behavior of FUS underlies poly-PR-induced DNA damage in amyotrophic lateral sclerosis.

  2023cites this paper
• Poly (ADP-ribose) polymerase 1 and neurodegenerative diseases: past, present, and future.

  2023cites this paper
• A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1G93A model of ALS

  2023cites this paper
• Pathomechanistic Networks of Motor System Injury in Amyotrophic Lateral Sclerosis

  2023cites this paper
• R-LOOPs on Short Tandem Repeat Expansion Disorders in Neurodegenerative Diseases

  2023cites this paper
• Protective Effects of Hexarelin and JMV2894 in a Human Neuroblastoma Cell Line Expressing the SOD1-G93A Mutated Protein

  2023cites this paper
• PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons

  2023cites this paper
• Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology

  2023cites this paper
• Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases

  2023cites this paper
• Mammalian telomeric RNA (TERRA) can be translated to produce valine–arginine and glycine–leucine dipeptide repeat proteins

  2023cites this paper
• Damaged DNA Is an Early Event of Neurodegeneration in Induced Pluripotent Stem Cell-Derived Motoneurons with UBQLN2P497H Mutation

  2022cites this paper
• CRISPR/Cas9 screen in human iPSC-derived cortical neurons identifies NEK6 as a novel disease modifier of C9orf72 poly(PR) toxicity

  2022cites this paper
• Epidrugs in Amyotrophic Lateral Sclerosis/Frontotemporal Dementia: Contextualizing a Role for Histone Kinase Inhibition in Neurodegenerative Disease.

  2022cites this paper
• The Complex Mechanisms by Which Neurons Die Following DNA Damage in Neurodegenerative Diseases

  2022cites this paper
• APE1/Ref-1 Role in Inflammation and Immune Response

  2022cites this paper
• Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship

  2022cites this paper
• Tracing brain genotoxic stress in Parkinson’s disease with a novel single-cell genetic sensor

  2022cites this paper
• DNA Damage, Defective DNA Repair, and Neurodegeneration in Amyotrophic Lateral Sclerosis

  2022cites this paper
• Nuclear RNA transcript levels modulate nucleocytoplasmic distribution of ALS/FTD-associated protein FUS

  2022cites this paper
• Identification of gene fusions associated with amyotrophic lateral sclerosis

  2022cites this paper
• Telomere Attrition in Induced Pluripotent Stem Cell-Derived Neurons From ALS/FTD-Related C9ORF72 Repeat Expansion Carriers

  2022cites this paper
• The Role of DNA Damage in Neural Plasticity in Physiology and Neurodegeneration

  2022cites this paper
• Activated or Impaired: An Overview of DNA Repair in Neurodegenerative Diseases

  2022cites this paper
• ROS scavengers decrease γH2ax spots in motor neuronal nuclei of ALS model mice in vitro

  2022cites this paper
• C9orf72 functions in the nucleus to regulate DNA damage repair

  2022cites this paper
• A candidate protective factor in amyotrophic lateral sclerosis: heterogenous nuclear ribonucleoprotein G

  2022cites this paper
• Unraveling the role of relative telomere length and CAG expansion on initial symptoms of juvenile Huntington disease

  2022cites this paper
• Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation

  2022cites this paper
• DNA damage as a mechanism of neurodegeneration in ALS and a contributor to astrocyte toxicity

  2021influential citation
• HnRNP G Reduces Neuron Death in Amyotrophic Lateral Sclerosis by Preventing Abnormal TDP-43 Accumulation

  2021cites this paper
• Role of Hydrazine-Related Chemicals in Cancer and Neurodegenerative Disease.

  2021cites this paper
• ZNF598 co-translationally titrates poly(GR) protein implicated in the pathogenesis of C9ORF72-associated ALS/FTD

  2021cites this paper
• Modeling C9orf72-Related Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Drosophila

  2021cites this paper
• Biomolecular Modifications Linked to Oxidative Stress in Amyotrophic Lateral Sclerosis: Determining Promising Biomarkers Related to Oxidative Stress

  2021cites this paper
• Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology

  2021cites this paper
• p53 Transactivation Domain Mediates Binding and Phase Separation with Poly-PR/GR

  2021cites this paper
• Epigenetic Small Molecules Rescue Nucleocytoplasmic Transport and DNA Damage Phenotypes in C9ORF72 ALS/FTD

  2021influential citation
• The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age

  2021cites this paper
• Adenosine deaminase, not immune to a mechanistic rethink in central nervous system disorders?

  2021cites this paper
• DNA Damage and Repair Deficiency in ALS/FTD-Associated Neurodegeneration: From Molecular Mechanisms to Therapeutic Implication

  2021cites this paper
• Faster Deep Ensemble Averaging for Quantification of DNA Damage from Comet Assay Images With Uncertainty Estimates

  2021cites this paper
• Unraveling molecular biology of C9ORF72 repeat expansions in amyotrophic lateral sclerosis-frontotemporal dementia: Implications for therapy

  2021cites this paper
• p53 is a central regulator driving neurodegeneration caused by C9orf72 poly(PR).

  2021cites this paper
• Emerging Perspectives on Dipeptide Repeat Proteins in C9ORF72 ALS/FTD

  2021cites this paper
• Emerging Evidence Highlighting the Importance of Redox Dysregulation in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS)

  2021cites this paper
• Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

  2021cites this paper
• The nuclear ubiquitin ligase adaptor SPOP is a conserved regulator of C9orf72 dipeptide toxicity

  2021cites this paper
• Multiple ways to a dead end: diverse mechanisms by which ALS mutant genes induce cell death

  2021cites this paper
• The PARP Way to Epigenetic Changes

  2021influential citation
• Altered Phase Separation and Cellular Impact in C9orf72-Linked ALS/FTD

  2021cites this paper
• Coping with RNA damage with a focus on APE1, a BER enzyme at the crossroad between DNA damage repair and RNA processing/decay.

  2021cites this paper
• Molecular mechanisms underlying nucleotide repeat expansion disorders

  2021cites this paper
• Spatiotemporal dynamics of γH2AX in the mouse brain after acute irradiation at different postnatal days with special reference to the dentate gyrus of the hippocampus

  2021cites this paper
• LSM12-EPAC1 defines a neuroprotective pathway that sustains the nucleocytoplasmic RAN gradient

  2020cites this paper
• Architecture of The Human Ape1 Interactome Defines Novel Cancers Signatures

  2020cites this paper
• Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

  2020cites this paper
• The role of DNA damage response in amyotrophic lateral sclerosis

  2020cites this paper
• Insights into disease mechanisms and potential therapeutics for C9orf72-related amyotrophic lateral sclerosis/frontotemporal dementia.

  2020cites this paper
• Impaired NHEJ repair in amyotrophic lateral sclerosis is associated with TDP-43 mutations

  2020cites this paper
• Neuronal Transcriptome from C9orf72 Repeat Expanded Human Tissue is Associated with Loss of C9orf72 Function

  2020cites this paper
• Role of the C9ORF72 Gene in the Pathogenesis of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

  2020influential citation
• Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development

  2020influential citation
• Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD

  2020cites this paper