Genes & Development: October 2013

A SUMO-dependent interaction between Senataxin and the exosome ... targets the exosome to sites of transcription-induced DNA damage.

Published: Genes Dev. October 15, 2013 27: 2227-2232. @ Patricia Richard. DOI:10.1101/gad.224923.113.

Authors: Patricia Richard, Shuang Feng, James L. Manley. Department of Biological Sciences, Columbia University, New York, NY.

Link to article: http://genesdev.cshlp.org/content/27/20/2227.long

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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