2. Academic Validation
  3. 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

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

  • Genes Dev. 2013 Oct 15;27(20):2227-32. doi: 10.1101/gad.224923.113.
Patricia Richard 1,  Shuang Feng,  James L Manley
Affiliations

Affiliation

  • 1 Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
PMID: 24105744 DOI: 10.1101/gad.224923.113
Abstract

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.

Keywords

Senataxin; exosome; sumoylation.

Figures