[P3-148]: A NOVEL SMART PEPTIDE REPRESENTING A 16-AMINO-ACID HUMAN TELOMERASE REVERSE TRANSCRIPTASE SEQUENCE HAS POSITIVE EFFECTS IN IN-VITRO AND IN-VIVO MODELS OF ALZHEIMER's DISEASE BY INCREASING TELOMERE LENGTH

2017 ◽  
Vol 13 (7S_Part_20) ◽  
pp. P991-P992
Author(s):  
Seong-Ho Koh ◽  
Hojin Choi ◽  
Hyun-Hee Park ◽  
Kyu-Yong Lee ◽  
Young J. Lee ◽  
...  
Keyword(s):  
Amino Acid ◽  
Telomere Length ◽  
Telomerase Reverse Transcriptase ◽  
Reverse Transcriptase Sequence ◽  
Human Telomerase Reverse Transcriptase ◽  
In Vivo Models ◽  
Positive Effects ◽  
Human Telomerase

scholarly journals Identification of human TERT elements necessary for telomerase recruitment to telomeres

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Jens C Schmidt ◽  
Andrew B Dalby ◽  
Thomas R Cech
Keyword(s):  
Dna Sequences ◽  
Repetitive Dna Sequences ◽  
Telomerase Reverse Transcriptase ◽  
Human Chromosomes ◽  
Human Telomerase Reverse Transcriptase ◽  
Interaction Interface ◽  
Ob Fold ◽  
Human Telomerase

Human chromosomes terminate in telomeres, repetitive DNA sequences bound by the shelterin complex. Shelterin protects chromosome ends, prevents recognition by the DNA damage machinery, and recruits telomerase. A patch of amino acids, termed the TEL-patch, on the OB-fold domain of the shelterin component TPP1 is essential to recruit telomerase to telomeres. In contrast, the site on telomerase that interacts with the TPP1 OB-fold is not well defined. In this study, we identify separation-of-function mutations in the TEN-domain of human telomerase reverse transcriptase (hTERT) that disrupt the interaction of telomerase with TPP1 in vivo and in vitro but have very little effect on the catalytic activity of telomerase. Suppression of a TEN-domain mutation with a compensatory charge-swap mutation in the TEL-patch indicates that their association is direct. Our findings define the interaction interface required for telomerase recruitment to telomeres, an important step towards developing modulators of this interaction as therapeutics for human disease.

scholarly journals Human Telomerase Reverse Transcriptase (hTERT) Q169 Is Essential for Telomerase Function In Vitro and In Vivo

PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7176 ◽  
Author(s):  
Haley D. M. Wyatt ◽  
Allison R. Tsang ◽  
Deirdre A. Lobb ◽  
Tara L. Beattie
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Human Telomerase

scholarly journals Functional Multimerization of the Human Telomerase Reverse Transcriptase

2001 ◽  
Vol 21 (18) ◽  
pp. 6151-6160 ◽  
Author(s):  
Tara L. Beattie ◽  
Wen Zhou ◽  
Murray O. Robinson ◽  
Lea Harrington
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Human Telomerase Reverse Transcriptase ◽  
Catalytic Core ◽  
Cell Extracts ◽  
Human Telomerase

ABSTRACT The telomerase enzyme exists as a large complex (∼1,000 kDa) in mammals and at minimum is composed of the telomerase RNA and the catalytic subunit telomerase reverse transcriptase (TERT). In Saccharomyces cerevisiae, telomerase appears to function as an interdependent dimer or multimer in vivo (J. Prescott and E. H. Blackburn, Genes Dev. 11:2790–2800, 1997). However, the requirements for multimerization are not known, and it remained unclear whether telomerase exists as a multimer in other organisms. We show here that human TERT (hTERT) forms a functional multimer in a rabbit reticulocyte lysate reconstitution assay and in human cell extracts. Two separate, catalytically inactive TERT proteins can complement each other in trans to reconstitute catalytic activity. This complementation requires the amino terminus of one hTERT and the reverse transcriptase and C-terminal domains of the second hTERT. The telomerase RNA must associate with only the latter hTERT for reconstitution of telomerase activity to occur. Multimerization of telomerase also facilitates the recognition and elongation of substrates in vitro and in vivo. These data suggest that the catalytic core of human telomerase may exist as a functionally cooperative dimer or multimer in vivo.

Regulation And Effect Of Telomerase And Telomeric Length In Stem Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Basak Celtikci ◽  
Gulnihal Kulaksiz Erkmen ◽  
Zeliha Gunnur Dikmen
Keyword(s):  
Telomere Length ◽  
Somatic Cells ◽  
Telomere Maintenance ◽  
The Other ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Telomere Shortening ◽  
Maintenance Mechanism ◽  
Associated Diseases ◽  
Human Telomerase

: Telomeres are the protective end caps of eukaryotic chromosomes and they decide the proliferative lifespan of somatic cells, as the guardians of the cell replication. Telomere length in leucocytes reflects telomere length in other somatic cells. Leucocyte telomere length can be a biomarker of human ageing. The risk of diseases, which are associated with reduced cell proliferation and tissue degeneration, including aging or aging-associated diseases, such as dyskeratosis congenita, cardiovascular diseases, pulmonary fibrosis and aplastic anemia, are correlated with an increase in short telomeres. On the other hand, the risk of diseases, which are associated with increased proliferative growth, including major cancers, is correlated with long telomeres. In most of the cancers, a telomere maintenance mechanism during DNA replication is essential. The reactivation of the functional ribonucleoprotein holoenzyme complex [telomerase] starts the cascade from normal and premalignant somatic cells to advanced malignant cells. Telomerase is overexpressed during the development of cancer and embryonic stem cells, through controlling genome integrity, cancer formation and stemness. Cancer cells have mechanisms to maintain telomeres to avoid initiation of cellular senescence or apoptosis, and halting cell division by critically short telomeres. Modulation of the human telomerase reverse transcriptase is the ratelimiting step for the production of functional telomerase and the telomere maintenance. Human telomerase reverse transcriptase promoter promotes its gene expression only in tumor cells, but not in normal cells. Some cancers activate an alternative lengthening of telomeres maintenance mechanism via DNA recombination to unshorten their telomeres. Not only heritability but also oxidative stress, inflammation, environmental factors, and therapeutic interventions have an effect on telomere shortening, explaining the variability in telomere length across individuals. There have been a large number of publications, which correlate human diseases with progressive telomere shortening. Telomere length of an individual at birth is also important to follow up telomere shortening, and it can be used as biomarkers for healthy aging. On the other hand, understanding of cellular stress factors, which affect stem cell behavior, will be useful in regeneration or treatment in cancer and age-associated diseases. In this review, we will understand the connection between stem cell and telomere biology, cancer, and aging-associated diseases. This connection may be useful for discovering novel drug targets and improve outcomes for patients having cancer and aging-associated diseases.

ESTABLISHMENT OF AN IN VIVO MENINGIOMA MODEL WITH HUMAN TELOMERASE REVERSE TRANSCRIPTASE

Neurosurgery ◽  
2007 ◽  
Vol 60 (4) ◽  
pp. 750-760 ◽  
Author(s):  
Theresa G. Cargioli ◽  
Hasan C. Ugur ◽  
Naren Ramakrishna ◽  
Jennifer Chan ◽  
Peter M. Black ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Human Telomerase

Bioflavonoids protect cells against halogenated boroxine-induced genotoxic damage by upregulation of hTERT expression

2019 ◽  
Vol 74 (5-6) ◽  
pp. 125-129 ◽  
Author(s):  
Maida Hadzic ◽  
Sanin Haveric ◽  
Anja Haveric ◽  
Naida Lojo-Kadric ◽  
Borivoj Galic ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Housekeeping Genes ◽  
Inhibitory Effects ◽  
Human Telomerase Reverse Transcriptase ◽  
Cycle Progression ◽  
Genotoxic Damage ◽  
Malignant Skin ◽  
Human Telomerase

Abstract Plant bioflavonoids are widely present in the human diet and have various protective properties. In this study, we have demonstrated the capacity of delphinidin and luteolin to increase human telomerase reverse transcriptase (hTERT) expression level and act as protective agents against halogenated boroxine-induced genotoxic damage. Halogenated boroxine K2(B3O3F4OH) (HB), is a novel compound with potential for the treatment of both benign and malignant skin changes. In vivo and in vitro studies have confirmed the inhibitory effects of HB on carcinoma cell proliferation and cell cycle progression as well as enzyme inhibition. However, minor genotoxic effects of HB are registered in higher applied concentrations, but those can be suppressed by in vitro addition of delphinidin and luteolin in appropriate concentrations. Fresh peripheral blood samples were cultivated for 72 h followed by independent and concomitant treatments of HB with luteolin or delphinidin. We analyzed the differences in relative hTERT expression between series of treatments compared with controls, which were based on normalized ratios with housekeeping genes. The obtained results have shown that selected bioflavonoids induce upregulation of hTERT that may contribute to the repair of genotoxic damage in vitro.

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