Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence

Autoři: Tina Wagner aff001;  Lara Pérez-Martínez aff002;  René Schellhaas aff002;  Marta Barrientos-Moreno aff003;  Merve Öztürk aff002;  Félix Prado aff003;  Falk Butter aff002;  Brian Luke aff001
Působiště autorů: Institute of Developmental Biology and Neurobiology (IDN), Johannes Gutenberg-Universität, Mainz, Germany aff001;  Institute of Molecular Biology (IMB) gGmbH, Mainz, Germany aff002;  Department of Genome Biology, Andalusian Molecular Biology and Regenerative Medicine Center (CABIMER), CSIC-University of Seville-University Pablo de Olavide, Seville, Spain aff003
Vyšlo v časopise: Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence. PLoS Genet 16(12): e1008603. doi:10.1371/journal.pgen.1008603
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008603


Telomeres 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.

Klíčová slova:

DNA damage – Histones – Chromatin – Polymerase chain reaction – Protein folding – Saccharomyces cerevisiae – Telomeres – Yeast


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