In Sen1, the N-terminus has shown interactions with the C-terminal domain of RNA polymerase II, ribonuclease III, and NER factor Rad2/XPG.

However, based on current research and examining homologs of SETX, senataxin is thought to play an important role in resolving R-loops, transcription termination, and maintaining genome stability by being an essential component of the DNA-damage response (DDR).

A large amount of R-loops are found at the 3’ end of some mammalian genes, after poly-adenylation sites.

The R-loops are thought to be involved in transcription termination by stalling RNA polymerase II.

[18] In ALS4 cells, SETX are mutated to have more helicase function, resulting in lower R-loop levels then usual, which causes abnormal TGF-β signaling and causes neuron death.

[19] AOA2 cells show senataxin loss of function and abnormally high R-loop levels.