SUMOylated Senataxin functions in genome stability, RNA degradation, and stress granule disassembly, and is linked with inherited ataxia and motor neuron disease.

ABSTRACT:

Background

Senataxin (SETX) is a DNA/RNA helicase critical for neuron survival. SETX mutations underlie two inherited neurodegenerative diseases: Ataxia with Oculomotor Apraxia type 2 (AOA2) and Amyotrophic Lateral Sclerosis type 4 (ALS4).

Methods

This review examines SETX key cellular processes and we hypothesize that SETX requires SUMO posttranslational modification to function properly.

Results

SETX is localized to distinct foci during S-phase of the cell cycle, and these foci represent sites of DNA polymerase/RNA polymerase II (RNAP) collision, as they co-localize with DNA damage markers 53BP1 and H2AX. At such sites, SETX directs incomplete RNA transcripts to the nuclear exosome for degradation via interaction with exosome component 9 (Exosc9), a key component of

SUBMITTER: Bennett CL 

PROVIDER: S-EPMC8683630 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature