Senataxin (E9Z9F) Rabbit mAb #83407

Senataxin is a ubiquitously expressed RNA-DNA helicase encoded by the SETX gene. Senataxin is well known for resolving RNA-DNA hybrid structures known as R-loops, which can form during gene transcription when the template DNA strand hybridizes with nascent mRNA (1). Senataxin is also recruited to DNA double-strand breaks (DSBs) on active genes, where it promotes cell survival and prevents translocations (2). Although R-loops may positively regulate gene expression under certain conditions, unresolved R-loops can promote DNA damage and have been linked to neurodegenerative disorders (3). Indeed, senataxin mutations are the root cause of the neurological conditions ataxia with oculomotor apraxia type 2 (AOA2) and juvenile amyotrophic lateral sclerosis (ALS4) (4-7). Senataxin dysregulation has also been observed in several types of cancer, where it may play a tumor suppressive role (8). Interestingly, loss of senataxin has been found to cause accumulation of RNA-DNA hybrids in the cytoplasm, consequently promoting an innate immune response via cGAS and IRF3 (9). This innate immune activation could provide an additional link between senataxin dysfunction and disease (9).