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R-loop-derived cytoplasmic RNA-DNA hybrids activate an immune response.
Crossley MP, Song C, Bocek MJ, Choi JH, Kousouros JN, Sathirachinda A, Lin C, Brickner JR, Bai G, Lans H, Vermeulen W, Abu-Remaileh M, Cimprich KA. Crossley MP, et al. Nature. 2023 Jan;613(7942):187-194. doi: 10.1038/s41586-022-05545-9. Epub 2022 Dec 21. Nature. 2023. PMID: 36544021 Free PMC article.
When nuclear R-loops were perturbed by depleting the RNA-DNA helicase senataxin (SETX) or the breast cancer gene BRCA1 (refs. (5-7)), we observed XPG- and XPF-dependent cytoplasmic hybrid formation. ...Excised hybrids and an R-loop-induced innate immune response wer …
When nuclear R-loops were perturbed by depleting the RNA-DNA helicase senataxin (SETX) or the breast cancer gene BRCA1 (refs. …
R-Loop Analysis by Dot-Blot.
Ramirez P, Crouch RJ, Cheung VG, Grunseich C. Ramirez P, et al. J Vis Exp. 2021 Jan 22;(167):10.3791/62069. doi: 10.3791/62069. J Vis Exp. 2021. PMID: 33554969 Free PMC article.
This assay can be used in research and clinical settings to quantify R-loops and assess the effect of mutations in genes such as senataxin on R-loop abundance....
This assay can be used in research and clinical settings to quantify R-loops and assess the effect of mutations in genes such as senataxi …
Helicases in R-loop Formation and Resolution.
Yang S, Winstone L, Mondal S, Wu Y. Yang S, et al. J Biol Chem. 2023 Nov;299(11):105307. doi: 10.1016/j.jbc.2023.105307. Epub 2023 Sep 29. J Biol Chem. 2023. PMID: 37778731 Free PMC article. Review.
Thus, helicases possess unique positions for R-loop biogenesis: they utilize their strand-annealing activity to promote the hybridization of RNA to DNA, leading to the formation of R-loops; conversely, they utilize their unwinding activity to separate RNA-DNA hybrids and resolve …
Thus, helicases possess unique positions for R-loop biogenesis: they utilize their strand-annealing activity to promote the hybridization of …
Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4.
Campisi L, Chizari S, Ho JSY, Gromova A, Arnold FJ, Mosca L, Mei X, Fstkchyan Y, Torre D, Beharry C, Garcia-Forn M, Jiménez-Alcázar M, Korobeynikov VA, Prazich J, Fayad ZA, Seldin MM, De Rubeis S, Bennett CL, Ostrow LW, Lunetta C, Squatrito M, Byun M, Shneider NA, Jiang N, La Spada AR, Marazzi I. Campisi L, et al. Nature. 2022 Jun;606(7916):945-952. doi: 10.1038/s41586-022-04844-5. Epub 2022 Jun 22. Nature. 2022. PMID: 35732742 Free PMC article.
Patients with ALS4 show motor difficulties by the time that they are in their thirties, and most of them require devices to assist with walking by their fifties. ALS4 is caused by mutations in the senataxin gene (SETX). Here, using Setx knock-in mice that car …
Patients with ALS4 show motor difficulties by the time that they are in their thirties, and most of them require devices to assist with walk …
Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes.
Coutelier M, Hammer MB, Stevanin G, Monin ML, Davoine CS, Mochel F, Labauge P, Ewenczyk C, Ding J, Gibbs JR, Hannequin D, Melki J, Toutain A, Laugel V, Forlani S, Charles P, Broussolle E, Thobois S, Afenjar A, Anheim M, Calvas P, Castelnovo G, de Broucker T, Vidailhet M, Moulignier A, Ghnassia RT, Tallaksen C, Mignot C, Goizet C, Le Ber I, Ollagnon-Roman E, Pouget J, Brice A, Singleton A, Durr A; Spastic Paraplegia and Ataxia Network. Coutelier M, et al. JAMA Neurol. 2018 May 1;75(5):591-599. doi: 10.1001/jamaneurol.2017.5121. JAMA Neurol. 2018. PMID: 29482223 Free PMC article.
The most frequently mutated genes were SPG7 (n = 14), SACS (n = 8), SETX (n = 7), SYNE1 (n = 6), and CACNA1A (n = 6). The highest diagnostic rate was obtained for patients with an autosomal recessive CA with oculomotor apraxia-like phenotype (6 of 17 [35.3%]) or spastic at …
The most frequently mutated genes were SPG7 (n = 14), SACS (n = 8), SETX (n = 7), SYNE1 (n = 6), and CACNA1A (n = 6). The highest dia …
Senataxin RNA/DNA helicase promotes replication restart at co-transcriptional R-loops to prevent MUS81-dependent fork degradation.
Rao S, Andrs M, Shukla K, Isik E, König C, Schneider S, Bauer M, Rosano V, Prokes J, Müller A, Janscak P. Rao S, et al. Nucleic Acids Res. 2024 Sep 23;52(17):10355-10369. doi: 10.1093/nar/gkae673. Nucleic Acids Res. 2024. PMID: 39119900 Free PMC article.
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 SETX promotes replication fork progression by preventing R-loop accumulati …
Here, we report that the restart of R-loop-stalled replication forks via the MUS81-LIG4-ELL pathway requires senataxin (SETX), …
Hypoxia-induced SETX links replication stress with the unfolded protein response.
Ramachandran S, Ma TS, Griffin J, Ng N, Foskolou IP, Hwang MS, Victori P, Cheng WC, Buffa FM, Leszczynska KB, El-Khamisy SF, Gromak N, Hammond EM. Ramachandran S, et al. Nat Commun. 2021 Jun 17;12(1):3686. doi: 10.1038/s41467-021-24066-z. Nat Commun. 2021. PMID: 34140498 Free PMC article.
Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. The …
Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX …
Role of Senataxin in Amyotrophic Lateral Sclerosis.
Tsui A, Kouznetsova VL, Kesari S, Fiala M, Tsigelny IF. Tsui A, et al. J Mol Neurosci. 2023 Dec;73(11-12):996-1009. doi: 10.1007/s12031-023-02169-0. Epub 2023 Nov 20. J Mol Neurosci. 2023. PMID: 37982993 Review.
Amyotrophic lateral sclerosis (ALS) is a progressive, uncurable neurodegenerative disorder characterized by the degradation of motor neurons leading to muscle impairment, failure, and death. Senataxin, encoded by the SETX gene, is a human helicase protein whose muta …
Amyotrophic lateral sclerosis (ALS) is a progressive, uncurable neurodegenerative disorder characterized by the degradation of motor neurons …
133 results