Downloads provided by UsageCountsFUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress
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UKRI| Cellular and Pathological Responses to Chromosome DNA Single-Strand Breaks ,
UKRI| Amyotrophic Lateral Sclerosis and the DNA Damage Response
Martinez-Macias, Maria Isabel; Moore, Duncan A.Q.; Green, Ryan L.; Gomez-Herreros, Fernando; Naumann, Marcel; Hermann, Andreas; Van Damme, Philip; +2 Authors
Martinez-Macias, Maria Isabel; Moore, Duncan A.Q.; Green, Ryan L.; Gomez-Herreros, Fernando; Naumann, Marcel; Hermann, Andreas; Van Damme, Philip; Hafezparast, Majid; Caldecott, Keith W.;
FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress
FUS (fused in sarcoma) plays a key role in several steps of RNA metabolism, and dominant mutations in this protein are associated with neurodegenerative diseases. Here, we show that FUS is a component of the cellular response to topoisomerase I (TOP1)–induced DNA breakage; relocalising to the nucleolus in response to RNA polymerase II (Pol II) stalling at sites of TOP1-induced DNA breaks. This relocalisation is rapid and dynamic, reversing following the removal of TOP1-induced breaks and coinciding with the recovery of global transcription. Importantly, FUS relocalisation following TOP1-induced DNA breakage is associated with increased FUS binding at sites of RNA polymerase I transcription in ribosomal DNA and reduced FUS binding at sites of RNA Pol II transcription, suggesting that FUS relocates from sites of stalled RNA Pol II either to regulate pre-mRNA processing during transcriptional stress or to modulate ribosomal RNA biogenesis. Importantly, FUS-mutant patient fibroblasts are hypersensitive to TOP1-induced DNA breakage, highlighting the possible relevance of these findings to neurodegeneration.
Spain, Germany, Belgium
- Spanish National Research Council Spain
- University of Sussex United Kingdom
- University of Seville Spain
- University of Sussex
- Université Catholique de Louvain Belgium
Life Sciences & Biomedicine - Other Topics, Transcription, Genetic, DNA Repair, TDP-43, metabolism [DNA Topoisomerases, Type I], ADN, metabolism [Neural Stem Cells], Q1, AMYOTROPHIC-LATERAL-SCLEROSIS, Mice, Neural Stem Cells, RNA Polymerase I, DNA Breaks, Double-Stranded, TOP1 protein, human, Research Articles, metabolism [RNA-Binding Protein FUS], Metabolismo, Neurons, ROLES, BINDING PROTEINS, Q, FUS protein, mouse, Brain, metabolism [RNA Polymerase I], Chromatin, ARN, genetics [Amyotrophic Lateral Sclerosis], DNA Topoisomerases, Type I, metabolism [Neurons], Proteínas, metabolism [RNA Polymerase II], COMPLEXES, Pacientes, RNA Polymerase II, Life Sciences & Biomedicine, FUS/TLS, metabolism [Fibroblasts], metabolism [Chromatin], INSTABILITY, RNA-POLYMERASE-II, genetics [Mutation], Q0179.9, embryology [Brain], Animals, Humans, pathology [Amyotrophic Lateral Sclerosis], Biology, SPINOCEREBELLAR ATAXIA, Science & Technology, Binding Sites, Mutación, MUTATIONS, 31 Biological sciences, cytology [Brain], Amyotrophic Lateral Sclerosis, 32 Biomedical and clinical sciences, FUS protein, human, Fibroblasts, A549 Cells, Hela Cells, Mutation, RNA-Binding Protein FUS, Mutant Proteins, genetics [RNA-Binding Protein FUS], HeLa Cells, ddc: ddc:570
Life Sciences & Biomedicine - Other Topics, Transcription, Genetic, DNA Repair, TDP-43, metabolism [DNA Topoisomerases, Type I], ADN, metabolism [Neural Stem Cells], Q1, AMYOTROPHIC-LATERAL-SCLEROSIS, Mice, Neural Stem Cells, RNA Polymerase I, DNA Breaks, Double-Stranded, TOP1 protein, human, Research Articles, metabolism [RNA-Binding Protein FUS], Metabolismo, Neurons, ROLES, BINDING PROTEINS, Q, FUS protein, mouse, Brain, metabolism [RNA Polymerase I], Chromatin, ARN, genetics [Amyotrophic Lateral Sclerosis], DNA Topoisomerases, Type I, metabolism [Neurons], Proteínas, metabolism [RNA Polymerase II], COMPLEXES, Pacientes, RNA Polymerase II, Life Sciences & Biomedicine, FUS/TLS, metabolism [Fibroblasts], metabolism [Chromatin], INSTABILITY, RNA-POLYMERASE-II, genetics [Mutation], Q0179.9, embryology [Brain], Animals, Humans, pathology [Amyotrophic Lateral Sclerosis], Biology, SPINOCEREBELLAR ATAXIA, Science & Technology, Binding Sites, Mutación, MUTATIONS, 31 Biological sciences, cytology [Brain], Amyotrophic Lateral Sclerosis, 32 Biomedical and clinical sciences, FUS protein, human, Fibroblasts, A549 Cells, Hela Cells, Mutation, RNA-Binding Protein FUS, Mutant Proteins, genetics [RNA-Binding Protein FUS], HeLa Cells, ddc: ddc:570
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).25 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10% views 36 downloads 62 - 36views62downloads
selected citations
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These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Citations provided by BIP!popularityPopularity provided by BIP!
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
Popularity provided by BIP!influenceInfluence provided by BIP!
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Influence provided by BIP!impulseImpulse provided by BIP!
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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