Wagner, TinaPérez-Martínez, LaraSchellhaas, RenéBarrientos-Moreno, MartaÖztürk, MervePrado, FélixButter, FalkLuke, Brian2022-07-112022-07-112020-12-28Wagner T, Pérez-Martínez L, Schellhaas R, Barrientos-Moreno M, Öztürk M, Prado F, et al. Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence. PLoS Genet. 2020 Dec 28;16(12):e1008603http://hdl.handle.net/10668/3774Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a distinct telomeric chromatin environment is a major requirement for the folding of yeast telomeres. We demonstrate that telomeres are not folded when cells enter replicative senescence, which occurs independently of short telomere length. Indeed, Sir2, Sin3 and Set2 protein levels are decreased during senescence and their absence may thereby prevent telomere folding. Additionally, we show that the homologous recombination machinery, including the Rad51 and Rad52 proteins, as well as the checkpoint component Rad53 are essential for establishing the telomere fold-back structure. This study outlines a method to interrogate telomere-subtelomere interactions at a single unmodified yeast telomere. Using this method, we provide insights into how the spatial arrangement of the chromosome end structure is established and demonstrate that telomere folding is compromised throughout replicative senescence.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ChromatinTelomereChromosomesSaccharomyces cerevisiaeDNA DamageCellular SenescenceRad52 DNA Repair and Recombination ProteinCromatinaTelómeroCromosomasDaño del ADNSenescencia celularProteína recombinante y reparadora de ADN Rad52Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::Histone DeacetylasesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::One-Carbon Group Transferases::MethyltransferasesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Recombinases::Rec A Recombinases::Rad51 RecombinaseMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Rad52 DNA Repair and Recombination ProteinMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Repressor ProteinsMedical Subject Headings::Organisms::Eukaryota::Fungi::Yeasts::Saccharomyces::Saccharomyces cerevisiaeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Fungal Proteins::Saccharomyces cerevisiae ProteinsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Fungal Proteins::Saccharomyces cerevisiae Proteins::Silent Information Regulator Proteins, Saccharomyces cerevisiaeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Sirtuins::Sirtuin 2Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cell Nucleus::Cell Nucleus Structures::Intranuclear Space::Chromosomes::Chromosome Structures::TelomereMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Cell Division::Telomere HomeostasisMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Replicationresearch article33370275Acceso abierto10.1371/journal.pgen.10086031553-7404PMC7793543