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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 nucleo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391683/ https://www.ncbi.nlm.nih.gov/pubmed/30808650 http://dx.doi.org/10.26508/lsa.201800222 |
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author | Martinez-Macias, Maria Isabel Moore, Duncan AQ Green, Ryan L Gomez-Herreros, Fernando Naumann, Marcel Hermann, Andreas Van Damme, Philip Hafezparast, Majid Caldecott, Keith W |
author_facet | Martinez-Macias, Maria Isabel Moore, Duncan AQ Green, Ryan L Gomez-Herreros, Fernando Naumann, Marcel Hermann, Andreas Van Damme, Philip Hafezparast, Majid Caldecott, Keith W |
author_sort | Martinez-Macias, Maria Isabel |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6391683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-63916832019-02-28 FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress Martinez-Macias, Maria Isabel Moore, Duncan AQ Green, Ryan L Gomez-Herreros, Fernando Naumann, Marcel Hermann, Andreas Van Damme, Philip Hafezparast, Majid Caldecott, Keith W Life Sci Alliance Research Articles 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. Life Science Alliance LLC 2019-02-26 /pmc/articles/PMC6391683/ /pubmed/30808650 http://dx.doi.org/10.26508/lsa.201800222 Text en © 2019 Martinez-Macias et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Martinez-Macias, Maria Isabel Moore, Duncan AQ 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 |
title | FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress |
title_full | FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress |
title_fullStr | FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress |
title_full_unstemmed | FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress |
title_short | FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress |
title_sort | fus (fused in sarcoma) is a component of the cellular response to topoisomerase i–induced dna breakage and transcriptional stress |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391683/ https://www.ncbi.nlm.nih.gov/pubmed/30808650 http://dx.doi.org/10.26508/lsa.201800222 |
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