ArticleHuman molecular genetics2012
The accumulation and not the specific activity of telomerase ribonucleoprotein determines telomere maintenance deficiency in X-linked dyskeratosis congenita.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Investigation of chromosome X inactivation and clinical phenotypes in female carriers of DKC1 mutations.American journal of hematology · 2016Trial
- Disease mutations in the N-terminal extension and α2'-helix of dyskerin do not abolish dimerization but disrupt binding to the telomerase RNA.RNA (New York, N.Y.) · 2026Article
- Recent progress in human telomerase structure and its therapeutic targeting.Frontiers in molecular biosciences · 2025Review
- The C-terminal extension of dyskerin is a dyskeratosis congenita mutational hotspot that modulates interaction with telomerase RNA and subcellular localization.Human molecular genetics · 2024Article
- Post-Transcriptional and Post-Translational Modifications in Telomerase Biogenesis and Recruitment to Telomeres.International journal of molecular sciences · 2023Review
- A novel cause ofEJHaem · 2021Article
- Regulation of human telomerase RNA biogenesis and localization.RNA biology · 2021Review
- Mild catalytic defects of tert rs61748181 polymorphism affect the clinical presentation of chronic obstructive pulmonary disease.Scientific reports · 2021Article
- GSE4 peptide suppresses oxidative and telomere deficiencies in ataxia telangiectasia patient cells.Cell death and differentiation · 2019Article
- N-terminal residues of human dyskerin are required for interactions with telomerase RNA that prevent RNA degradation.Nucleic acids research · 2019Article
- Homology Model and Docking-Based Virtual Screening for Ligands of Human Dyskerin as New Inhibitors of Telomerase for Cancer Treatment.International journal of molecular sciences · 2018Article
- Clinical heterogeneity in a family withPediatric reports · 2017Article
- Clonal hematopoiesis in patients with dyskeratosis congenita.American journal of hematology · 2016Article
- Unraveling the pathogenesis of Hoyeraal-Hreidarsson syndrome, a complex telomere biology disorder.British journal of haematology · 2015Review
- Article
- Defects in mTR stability and telomerase activity produced by the Dkc1 A353V mutation in dyskeratosis congenita are rescued by a peptide from the dyskerin TruB domain.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2012Article
- Article
- Molecular mechanisms of telomere biology disorders.The Journal of biological chemistryReview
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
X-linked dyskeratosis congenita (X-DC) is caused by mutations in the housekeeping nucleolar protein dyskerin. Amino acid changes associated with X-DC are remarkably heterogeneous. Peripheral mononuclear blood cells and fibroblasts isolated from X-DC patients harbor lower steady-state telomerase RNA (TER) levels and shorter telomeres than healthy age-matched controls. Previously, we showed that retroviral expression of recombinant TER, together with expression of recombinant telomerase reverse transcriptase, restored telomere maintenance and proliferative capacity in X-DC patient cells. Using rare X-DC isoforms (ΔL37 and A386T dyskerin), we showed that telomere maintenance defects observed in X-DC are solely due to decreased steady-state levels of TER. Disease-associated reductions in steady-state TER levels cause deficiencies in telomere maintenance. Here, we confirm these findings in other primary X-DC patient cell lines coding for the most common (A353V dyskerin) and more clinically severe (K314R and A353V dyskerin) X-DC isoforms. Using cell lines derived from these patients, we also examined the steady-state levels of other hinge-ACA motif RNAs and did not find differences in their in vivo accumulations. We show, for the first time, that purified telomerase holoenzyme complexes from different X-DC cells have normal catalytic activity. Our data confirm that dyskerin promotes TER stability in vivo, endorsing the development of TER supplementation strategies for the treatment of X-DC.
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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.