Journal ArticleDOI
Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence
Bettina Balk,André Maicher,Martina Dees,Julia Klermund,Sarah Luke-Glaser,Katharina Bender,Brian Luke +6 more
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TLDR
It is shown that RNA-DNA hybrids form at telomeres and are removed by RNase H enzymes in the budding yeast, Saccharomyces cerevisiae, and 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.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.read more
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Dissertation
Regulation of Telomere Length and its Maintenance in the Absence of Telomerase in Budding Yeast Saccharomyces Cerevisiae
TL;DR: It is demonstrated that in addition to the genetic components, initial telomere length and the timing of senescence are essential factors that influence telomerase negative survival.
Journal ArticleDOI
Spontaneous DNA-RNA hybrids: differential impacts throughout the cell cycle.
TL;DR: A large body of research supports that transcription plays a major role among the many sources of replicative stress contributing to genome instability, and three major DDR pathways were defined to participate in the protection against DNA-RNA hybrids.
Journal ArticleDOI
Telomere organization and the interstitial telomeric sites involvement in insects and vertebrates chromosome evolution
Marcelo Ricardo Vicari,Daniel Pacheco Bruschi,Diogo Cavalcanti Cabral-de-Mello,Viviane Nogaroto +3 more
TL;DR: In this paper , the relation between interstitial telomeric sequences (ITS) and chromosome rearrangements was observed in insects and vertebrates, demonstrating different types of genome organization and distribution.
Journal ArticleDOI
Telomeric Double Strand Breaks in G1 Human Cells Facilitate Formation of 5′ C-Rich Overhangs and Recruitment of TERRA
Christopher B. Nelson,Taghreed M Alturki,Jared J. Luxton,Lynn Taylor,David G. Maranon,Keiko Muraki,John P. Murnane,Susan M. Bailey +7 more
TL;DR: In this article, the authors characterized the human cellular response to targeted telomeric double-strand breaks (DSBs) in telomerase-positive and non-homologous end-joining (c-NHEJ) at telomeres, specifically in G1 phase.
References
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Journal ArticleDOI
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
TL;DR: It is proposed that the novel telomere terminal transferase is involved in the addition of telomeric repeats necessary for the replication of chromosome ends in eukaryotes.
Journal ArticleDOI
Mammalian Telomeres End in a Large Duplex Loop
Jack D. Griffith,Laurey Comeau,Soraya Rosenfield,Rachel M. Stansel,Alessandro Bianchi,Heidi Moss,Titia de Lange +6 more
TL;DR: Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro, which may provide a general mechanism for the protection and replication of telomeres.
Journal ArticleDOI
Origin of concatemeric T7 DNA.
TL;DR: The observed concatemers of T7 DNA are consistent with replication schemes resulting in double-helical molecules with 3´ ended tails as discussed by the authors, and they can then join to form dimers which on further replication similarly form larger concatures.
Journal ArticleDOI
Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends.
TL;DR: It is demonstrated that mammalian telomeres are transcribed into telomeric repeat–containing RNA (TERRA), and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.
Journal ArticleDOI
An alternative pathway for yeast telomere maintenance rescues est1− senescence
TL;DR: It is shown that a minor subpopulation of est1- survivors arise as a result of the amplification and acquisition of subtelomeric elements (and their deletion derivatives) by a large number of telomeres, indicating that even when the primary pathway for telomere replication is defective, an alternative backup pathway can restore telomerre function and keep the cell alive.