2026-04-29T04:09:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/252482024-10-23T10:07:12Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16958

00925njm 22002777a 4500 dc Martinez-Macias, Maria Isabel author Moore, Duncan Aq author Green, Ryan L author Gomez-Herreros, Fernando author Naumann, Marcel author Hermann, Andreas author Van Damme, Philip author Hafezparast, Majid author Caldecott, Keith W author 2019-02-26 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. http://hdl.handle.net/10668/13629 https://hdl.handle.net/20.500.12105/25248 30808650 10.26508/lsa.201800222 2575-1077 Life science alliance FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I-induced DNA breakage and transcriptional stress.