ArticleCell cycle (Georgetown, Tex.)2014
Telomerase enzymatic component hTERT shortens long telomeres in human cells.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Effects of Resveratrol on Nonmelanoma Skin Cancer (NMSC): A Comprehensive Review.Food science & nutrition · 2024Review
- Connecting the Dots: Telomere Shortening and Rheumatic Diseases.Biomolecules · 2024Review
- Telomere length is an epigenetic trait - Implications for the use of telomerase-deficient organisms to model human disease.Disease models & mechanisms · 2024Article
- Article
- Improving the effectiveness of anti-aging modalities by using the constrained disorder principle-based management algorithms.Frontiers in aging · 2022Review
- Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers.International journal of epidemiology · 2019Article
- Fanconi anemia proteins in telomere maintenance.DNA repair · 2016Review
- Dimerization of SLX4 contributes to functioning of the SLX4-nuclease complex.Nucleic acids research · 2016Article
- Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian.Carcinogenesis · 2015Article
- SLX4 contributes to telomere preservation and regulated processing of telomeric joint molecule intermediates.Nucleic acids research · 2015Article
- Telomere length variation: A potential new telomere biomarker for lung cancer risk.Lung cancer (Amsterdam, Netherlands) · 2015Article
- Defective repair of uracil causes telomere defects in mouse hematopoietic cells.The Journal of biological chemistry · 2015Article
- Antiproliferative effect of the isoquinoline alkaloid papaverine in hepatocarcinoma HepG-2 cells--inhibition of telomerase and induction of senescence.Molecules (Basel, Switzerland) · 2014Article
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Telomere lengths are tightly regulated within a narrow range in normal human cells. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in elongating short telomeres. However, much about the molecular mechanisms of regulating excessively long telomeres is unknown. In this report, we demonstrated that the telomerase enzymatic component, hTERT, plays a dual role in the regulation of telomere length. It shortens excessively long telomeres and elongates short telomeres simultaneously in one cell, maintaining the optimal telomere length at each chromosomal end for efficient protection. This novel hTERT-mediated telomere-shortening mechanism not only exists in cancer cells, but also in primary human cells. The hTERT-mediated telomere shortening requires hTERT's enzymatic activity, but the telomerase RNA component, hTR, is not involved in that process. We found that expression of hTERT increases telomeric circular DNA formation, suggesting that telomere homologous recombination is involved in the telomere-shortening process. We further demonstrated that shelterin protein TPP1 interacts with hTERT and recruits hTERT onto the telomeres, suggesting that TPP1 might be involved in regulation of telomere shortening. This study reveals a novel function of hTERT in telomere length regulation and adds a new element to the current molecular model of telomere length maintenance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.