USP11 controls R-loops by regulating senataxin proteostasis.

Nature Communications
Mateusz JurgaSherif F El-Khamisy


R-loops are by-products of transcription that must be tightly regulated to maintain genomic stability and gene expression. Here, we describe a mechanism for the regulation of the R-loop-specific helicase, senataxin (SETX), and identify the ubiquitin specific peptidase 11 (USP11) as an R-loop regulator. USP11 de-ubiquitinates SETX and its depletion increases SETX K48-ubiquitination and protein turnover. Loss of USP11 decreases SETX steady-state levels and reduces R-loop dissolution. Ageing of USP11 knockout cells restores SETX levels via compensatory transcriptional downregulation of the E3 ubiquitin ligase, KEAP1. Loss of USP11 reduces SETX enrichment at KEAP1 promoter, leading to R-loop accumulation, enrichment of the endonuclease XPF and formation of double-strand breaks. Overexpression of KEAP1 increases SETX K48-ubiquitination, promotes its degradation and R-loop accumulation. These data define a ubiquitination-dependent mechanism for SETX regulation, which is controlled by the opposing activities of USP11 and KEAP1 with broad applications for cancer and neurological disease.


Feb 11, 2004·Nature Genetics·Maria-Céu MoreiraMichel Koenig
Feb 14, 2004·Science·Kenneth D WestoverRoger D Kornberg
Apr 24, 2004·American Journal of Human Genetics·Ying-Zhang ChenPhillip F Chance
Nov 3, 2004·Trends in Molecular Medicine·Hozumi Motohashi, Masayuki Yamamoto
Mar 15, 2006·Nature Cell Biology·Tony T HuangAlan D D'Andrea
Oct 11, 2007·The Journal of Biological Chemistry·Ok-Hee LeeAnil K Jaiswal
Nov 6, 2007·Current Biology : CB·Francesco NicassioElisabetta Citterio
Apr 17, 2008·Genes & Development·Junya KawauchiNick J Proudfoot
Jul 10, 2012·Open Biology·Mazin A Al-SalihiGopal P Sapkota
Feb 19, 2013·Molecular Cell·Stephen P Jackson, Daniel Durocher
Feb 4, 2014·Nature Communications·Hsin-Chieh WuRuey-Hwa Chen
Dec 9, 2014·Cell Death and Differentiation·A H Lund
Nov 20, 2015·PLoS Genetics·María L García-RubioAndrés Aguilera
Dec 10, 2015·Nature·Alexandre OrthweinDaniel Durocher
Mar 21, 2017·The EMBO Journal·Dana HodrojDomenico Maiorano
May 13, 2017·Annual Review of Biochemistry·Tycho E T Mevissen, David Komander
Jul 18, 2017·Nature Neuroscience·Callum WalkerSherif F El-Khamisy
Sep 21, 2017·Nature Reviews. Molecular Cell Biology·Michael Rape
Apr 17, 2018·Molecular Cell·Hannah E MischoStephen Buratowski
Jul 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Laurianne DanielGiuseppina Giglia-Mari

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