Hypoosmotic stress induces R loop formation in nucleoli and ATR/ATM-dependent silencing of nucleolar transcription.

Autor:	Velichko AK; Laboratory of Genome Stability, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.; Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia., Petrova NV; Laboratory of Genome Stability, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia., Luzhin AV; Laboratory of Genome Stability, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia., Strelkova OS; A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia., Ovsyannikova N; A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia., Kireev II; A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia.; V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, 117997 Moscow, Russia., Petrova NV; Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia., Razin SV; Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.; Department of Molecular Biology, Moscow State University, 119234 Moscow, Russia.; LFR2O, Institute Gustave Roussy, F-94805 Villejuif, France., Kantidze OL; Laboratory of Genome Stability, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.; LFR2O, Institute Gustave Roussy, F-94805 Villejuif, France.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2019 Jul 26; Vol. 47 (13), pp. 6811-6825.
DOI:	10.1093/nar/gkz436
Abstrakt:	The contribution of nucleoli to the cellular stress response has been discussed for over a decade. Stress-induced inhibition of RNA polymerase I-dependent transcription is hypothesized as a possible effector program in such a response. In this study, we report a new mechanism by which ribosomal DNA transcription can be inhibited in response to cellular stress. Specifically, we demonstrate that mild hypoosmotic stress induces stabilization of R loops in ribosomal genes and thus provokes the nucleoli-specific DNA damage response, which is governed by the ATM- and Rad3-related (ATR) kinase. Activation of ATR in nucleoli strongly depends on Treacle, which is needed for efficient recruitment/retention of TopBP1 in nucleoli. Subsequent ATR-mediated activation of ATM results in repression of nucleolar transcription. (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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