Faculty Opinions recommendation of DNA-PKcs is critical for telomere capping.

Telomeres are specialized high-order chromatin structures that cap the ends of eukaryotic chromosomes. In vertebrates, telomeric DNA is composed of repetitions of the TTAGGG hexanucleotide, is bound to a set of specific proteins, and is elongated by the reverse transcriptase enzyme telomerase. Telomerase activity is promptly detected in cells with an indefinite replicative potential, such as cancer cells, while is almost undetectable in normal cells, which are characterized by a limited life span. Mounting evidence indicates that the maintenance of telomere integrity and telomerase protect cells from apoptosis. Disruption of the telomere capping function and (or) telomerase inhibition elicit an apoptotic response in cancer cells, while restoration of telomerase activity in somatic cells confers resistance to apoptosis. The possible mechanisms linking telomeres, telomerase and apoptosis are discussed in this review, together with the impact of this field in anticancer research.Key words: telomeres, telomerase, telomeric proteins, apoptosis, tumorigenesis.

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A regulatory loop connecting WNT signaling and telomere capping: possible therapeutic implications for dyskeratosis congenita

Annals of the New York Academy of Sciences ◽

10.1111/nyas.13692 ◽

2018 ◽

Vol 1418 (1) ◽

pp. 56-68 ◽

Cited By ~ 7

Author(s):

Rafael Jesus Fernandez ◽

F. Brad Johnson

Keyword(s):

Wnt Signaling ◽

Dyskeratosis Congenita ◽

Therapeutic Implications ◽

Telomere Capping ◽

Regulatory Loop

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Repeated Evolution of Testis-Specific New Genes: The Case of Telomere-Capping Genes in Drosophila

International Journal of Evolutionary Biology ◽

10.1155/2012/708980 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Raphaëlle Dubruille ◽

Gabriel A. B. Marais ◽

Benjamin Loppin

Keyword(s):

Gene Family ◽

Specific Expression ◽

Functional Studies ◽

Evolutionary Forces ◽

New Genes ◽

Male Gametes ◽

Duplication Events ◽

New Gene ◽

Telomere Capping ◽

Specific Expression Pattern

Comparative genome analysis has allowed the identification of various mechanisms involved in gene birth. However, understanding the evolutionary forces driving new gene origination still represents a major challenge. In particular, an intriguing and not yet fully understood trend has emerged from the study of new genes: many of them show a testis-specific expression pattern, which has remained poorly understood. Here we review the case of such a new gene, which involves a telomere-capping gene family in Drosophila. hiphop and its testis-specific paralog K81 are critical for the protection of chromosome ends in somatic cells and male gametes, respectively. Two independent functional studies recently proposed that these genes evolved under a reproductive-subfunctionalization regime. The 2011 release of new Drosophila genome sequences from the melanogaster group of species allowed us to deepen our phylogenetic analysis of the hiphop/K81 family. This work reveals an unsuspected dynamic of gene birth and death within the group, with recurrent duplication events through retroposition mechanisms. Finally, we discuss the plausibility of different evolutionary scenarios that could explain the diversification of this gene family.

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Biological Activity of the G-Quadruplex Ligand RHPS4 (3,11-Difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate) Is Associated with Telomere Capping Alteration

Molecular Pharmacology ◽

10.1124/mol.104.001537 ◽

2004 ◽

Vol 66 (5) ◽

pp. 1138-1146 ◽

Cited By ~ 100

Author(s):

Carlo Leonetti ◽

Sarah Amodei ◽

Carmen D'Angelo ◽

Angela Rizzo ◽

Barbara Benassi ◽

...

Keyword(s):

Biological Activity ◽

G Quadruplex ◽

Telomere Capping

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The Telomere Capping Complex CST Has an Unusual Stoichiometry, Makes Multipartite Interaction with G-Tails, and Unfolds Higher-Order G-Tail Structures

PLoS Genetics ◽

10.1371/journal.pgen.1003145 ◽

2013 ◽

Vol 9 (1) ◽

pp. e1003145 ◽

Cited By ~ 25

Author(s):

Neal F. Lue ◽

Ruobo Zhou ◽

Lidia Chico ◽

Ninghui Mao ◽

Olga Steinberg-Neifach ◽

...

Keyword(s):

Higher Order ◽

Telomere Capping

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A Mutation in the STN1 Gene Triggers an Alternative Lengthening of Telomere-Like Runaway Recombinational Telomere Elongation and Rapid Deletion in Yeast

Molecular and Cellular Biology ◽

10.1128/mcb.25.18.8064-8073.2005 ◽

2005 ◽

Vol 25 (18) ◽

pp. 8064-8073 ◽

Cited By ~ 31

Author(s):

Shilpa Iyer ◽

Ashley D. Chadha ◽

Michael J. McEachern

Keyword(s):

Human Cancer ◽

Kluyveromyces Lactis ◽

High Rate ◽

Telomere Elongation ◽

Human Cancer Cells ◽

Alternative Lengthening ◽

Telomere Capping ◽

Synthetically Lethal ◽

Very High ◽

Novel Allele

ABSTRACT Some human cancer cells achieve immortalization by using a recombinational mechanism termed ALT (alternative lengthening of telomeres). A characteristic feature of ALT cells is the presence of extremely long and heterogeneous telomeres. The molecular mechanism triggering and maintaining this pathway is currently unknown. In Kluyveromyces lactis, we have identified a novel allele of the STN1 gene that produces a runaway ALT-like telomeric phenotype by recombination despite the presence of an active telomerase pathway. Additionally, stn1-M1 cells are synthetically lethal in combination with rad52 and display chronic growth and telomere capping defects including extensive 3′ single-stranded telomere DNA and highly elevated subtelomere gene conversion. Strikingly, stn1-M1 cells undergo a very high rate of telomere rapid deletion (TRD) upon reintroduction of STN1. Our results suggest that the protein encoded by STN1, which protects the terminal 3′ telomere DNA, can regulate both ALT and TRD.

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