title: Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence.
abstract: Although telomeres are heterochromatic, they are transcribed into noncoding telomeric repeat-containing RNA (TERRA). Here we show that RNA-DNA hybrids form at telomeres and are removed by RNase H enzymes in the budding yeast, Saccharomyces cerevisiae. In recombination-competent telomerase mutants, telomeric RNA-DNA hybrids promote recombination-mediated elongation events that delay the onset of cellular senescence. Reduction of TERRA and telomeric RNA-DNA-hybrid levels diminishes rates of recombination-mediated telomere elongation in cis. Overexpression of RNase H decreases telomere recombination rates and accelerates senescence in recombination-competent but not recombination-deficient cells. In contrast, in the absence of both telomerase and homologous recombination, accumulation of telomeric RNA-DNA hybrids leads to telomere loss and accelerated rates of cellular senescence. Therefore, the regulation of TERRA transcription and telomeric RNA-DNA-hybrid formation are important determinants of both telomere-length dynamics and proliferative potential after the inactivation of telomerase.
authors.affiliation: 1] Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Deutsches Krebsforschungszentrum (DKFZ)-ZMBH Alliance, Heidelberg, Germany. [2].
authors.forename: Bettina
authors.initials: B
authors.lastname: Balk
authors.forename: André
authors.initials: A
authors.lastname: Maicher
authors.forename: Martina
authors.initials: M
authors.lastname: Dees
authors.forename: Julia
authors.initials: J
authors.lastname: Klermund
authors.forename: Sarah
authors.initials: S
authors.lastname: Luke-Glaser
authors.forename: Katharina
authors.initials: K
authors.lastname: Bender
authors.forename: Brian
authors.initials: B
authors.lastname: Luke
mesh_terms: D000375:Aging / Q000235:genetics*; D004271:DNA, Fungal / Q000737:chemistry*; D009693:Nucleic Acid Hybridization; D012331:RNA, Fungal / Q000737:chemistry*; D011995:Recombination, Genetic; D016914:Ribonuclease H / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016615:Telomere
chemical_list: D004271:DNA, Fungal; D012331:RNA, Fungal; D016914:Ribonuclease H