Senataxin RNA/DNA helicase promotes replication restart at co-transcriptional R-loops to prevent MUS81-dependent fork degradation

Rao, Satyajeet; Andrs, Martin; Shukla, Kaustubh; Isik, Esin; König, Christiane; Schneider, Stefan; Bauer, Michael; Rosano, Vinicio; Prokes, Jiri; Müller, Anne; Janscak, Pavel

doi:10.1093/nar/gkae673

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Rao, S., Andrs, M., Shukla, K., Isik, E., König, C., Schneider, S., Bauer, M., Rosano, V., Prokes, J., Müller, A., & Janscak, P. (2024). Senataxin RNA/DNA helicase promotes replication restart at co-transcriptional R-loops to prevent MUS81-dependent fork degradation. Nucleic Acids Research, 52(17), 10355–10369. https://doi.org/10.1093/nar/gkae673

Abstract

Replication forks stalled at co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage-religation cycles mediated by MUS81 endonuclease and DNA ligase IV (LIG4), which presumably relieve the topological barrier generated by the transcription-replication conflict (TRC) and facilitate ELL-dependent reactivation of transcription. Here, we report that the restart of R-loop-stalled replication forks via the MUS81-LIG4-ELL pathway requires senataxin (SETX), a helicase that can unwind RNA:DNA hybrids. We found that S