A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage

Senataxin (SETX) is an RNA/DNA helicase implicated in transcription termination and the DNA damage response and is mutated in two distinct neurological disorders: AOA2 (ataxia oculomotor apraxia 2) and ALS4 (amyotrophic lateral sclerosis 4). Here we provide evidence that Rrp45, a subunit of the exos...

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Detalles Bibliográficos
Autores principales: Richard, Patricia, Feng, Shuang, Manley, James L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2013
Materias:
Research Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814643/
https://www.ncbi.nlm.nih.gov/pubmed/24105744
http://dx.doi.org/10.1101/gad.224923.113
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author Richard, Patricia
Feng, Shuang
Manley, James L.
author_facet Richard, Patricia
Feng, Shuang
Manley, James L.
author_sort Richard, Patricia
collection PubMed
description Senataxin (SETX) is an RNA/DNA helicase implicated in transcription termination and the DNA damage response and is mutated in two distinct neurological disorders: AOA2 (ataxia oculomotor apraxia 2) and ALS4 (amyotrophic lateral sclerosis 4). Here we provide evidence that Rrp45, a subunit of the exosome, associates with SETX in a manner dependent on SETX sumoylation. We show that the interaction and SETX sumoylation are disrupted by SETX mutations associated with AOA2 but not ALS4. Furthermore, Rrp45 colocalizes with SETX in distinct foci upon induction of transcription-related DNA damage. Our results thus provide evidence for a SUMO-dependent interaction between SETX and the exosome, disrupted in AOA2, that targets the exosome to sites of DNA damage.
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spelling pubmed-38146432014-04-15 A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage Richard, Patricia Feng, Shuang Manley, James L. Genes Dev Research Communication Senataxin (SETX) is an RNA/DNA helicase implicated in transcription termination and the DNA damage response and is mutated in two distinct neurological disorders: AOA2 (ataxia oculomotor apraxia 2) and ALS4 (amyotrophic lateral sclerosis 4). Here we provide evidence that Rrp45, a subunit of the exosome, associates with SETX in a manner dependent on SETX sumoylation. We show that the interaction and SETX sumoylation are disrupted by SETX mutations associated with AOA2 but not ALS4. Furthermore, Rrp45 colocalizes with SETX in distinct foci upon induction of transcription-related DNA damage. Our results thus provide evidence for a SUMO-dependent interaction between SETX and the exosome, disrupted in AOA2, that targets the exosome to sites of DNA damage. Cold Spring Harbor Laboratory Press 2013-10-15 /pmc/articles/PMC3814643/ /pubmed/24105744 http://dx.doi.org/10.1101/gad.224923.113 Text en © 2013 Richard et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research Communication
Richard, Patricia
Feng, Shuang
Manley, James L.
A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage
title A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage
title_full A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage
title_fullStr A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage
title_full_unstemmed A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage
title_short A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage
title_sort sumo-dependent interaction between senataxin and the exosome, disrupted in the neurodegenerative disease aoa2, targets the exosome to sites of transcription-induced dna damage
topic Research Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814643/
https://www.ncbi.nlm.nih.gov/pubmed/24105744
http://dx.doi.org/10.1101/gad.224923.113
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