دورية أكاديمية
The Rad53CHK1/CHK2-Spt21NPAT and Tel1ATM axes couple glucose tolerance to histone dosage and subtelomeric silencing
| العنوان: | The Rad53CHK1/CHK2-Spt21NPAT and Tel1ATM axes couple glucose tolerance to histone dosage and subtelomeric silencing |
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| المؤلفون: | Bruhn C., Ajazi A., Ferrari E., Lanz M. C., Batrin R., Choudhary R., Walvekar A., Laxman S., Longhese M. P., Fabre E., Smolka M. B., Foiani M. |
| المساهمون: | Bruhn, C, Ajazi, A, Ferrari, E, Lanz, M, Batrin, R, Choudhary, R, Walvekar, A, Laxman, S, Longhese, M, Fabre, E, Smolka, M, Foiani, M |
| بيانات النشر: | Nature Publishing Group GB |
| سنة النشر: | 2020 |
| المجموعة: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| مصطلحات موضوعية: | Acetylation, Ataxia Telangiectasia Mutated Protein, Cell Cycle Protein, Checkpoint Kinase 2, DNA Damage, DNA Repair, Gene Silencing, Glucose, Histone Deacetylase, Histone, Intracellular Signaling Peptides and Protein, Mutation, Phosphorylation, Protein-Serine-Threonine Kinase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Protein, Serine, Telomere, Transcription Factors |
| الوصف: | The DNA damage response (DDR) coordinates DNA metabolism with nuclear and non-nuclear processes. The DDR kinase Rad53CHK1/CHK2 controls histone degradation to assist DNA repair. However, Rad53 deficiency causes histone-dependent growth defects in the absence of DNA damage, pointing out unknown physiological functions of the Rad53-histone axis. Here we show that histone dosage control by Rad53 ensures metabolic homeostasis. Under physiological conditions, Rad53 regulates histone levels through inhibitory phosphorylation of the transcription factor Spt21NPAT on Ser276. Rad53-Spt21 mutants display severe glucose dependence, caused by excess histones through two separable mechanisms: dampening of acetyl-coenzyme A-dependent carbon metabolism through histone hyper-acetylation, and Sirtuin-mediated silencing of starvation-induced subtelomeric domains. We further demonstrate that repression of subtelomere silencing by physiological Tel1ATM and Rpd3HDAC activities coveys tolerance to glucose restriction. Our findings identify DDR mutations, histone imbalances and aberrant subtelomeric chromatin as interconnected causes of glucose dependence, implying that DDR kinases coordinate metabolism and epigenetic changes. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32814778; info:eu-repo/semantics/altIdentifier/wos/WOS:000565663200002; volume:11; issue:1; journal:NATURE COMMUNICATIONS; https://hdl.handle.net/10281/289010Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85089557421 |
| DOI: | 10.1038/s41467-020-17961-4 |
| الإتاحة: | https://doi.org/10.1038/s41467-020-17961-4Test https://hdl.handle.net/10281/289010Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.517106FE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-020-17961-4 |
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