Hypoosmotic stress induces R loop formation in nucleoli and ATR/ATM-dependent silencing of nucleolar transcription.
Nucleic Acids Res
; 47(13): 6811-6825, 2019 07 26.
Article
em En
| MEDLINE
| ID: mdl-31114877
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pressão Osmótica
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Transcrição Gênica
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DNA Ribossômico
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Proteínas Nucleares
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Proteínas de Transporte
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Nucléolo Celular
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Inativação Gênica
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Proteínas de Ligação a DNA
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Proteínas Mutadas de Ataxia Telangiectasia
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Estruturas R-Loop
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article