@article {2150,
	title = {The Rad53-Spt21 and Tel1 axes couple glucose tolerance to histone dosage and subtelomeric silencing.},
	journal = {Nat Commun},
	volume = {11},
	year = {2020},
	month = {2020 08 19},
	pages = {4154},
	abstract = {<p>The DNA damage response (DDR) coordinates DNA metabolism with nuclear and non-nuclear processes. The DDR kinase Rad53 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 Spt21 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 Tel1 and Rpd3 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.</p>
},
	keywords = {Acetylation, Ataxia Telangiectasia Mutated Proteins, Cell Cycle Proteins, Checkpoint Kinase 2, DNA Damage, DNA Repair, Gene Silencing, Glucose, Histone Deacetylases, Histones, Intracellular Signaling Peptides and Proteins, Mutation, Phosphorylation, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Serine, Telomere, Transcription Factors},
	issn = {2041-1723},
	doi = {10.1038/s41467-020-17961-4},
	author = {Bruhn, Christopher and Ajazi, Arta and Ferrari, Elisa and Lanz, Michael Charles and Batrin, Renaud and Choudhary, Ramveer and Walvekar, Adhish and Laxman, Sunil and Longhese, Maria Pia and Fabre, Emmanuelle and Smolka, Marcus Bustamente and Foiani, Marco}
}
