Редактирование: CTC1

CST complex subunit CTC1 (Conserved telomere maintenance component 1) (HBV DNAPTP1-transactivated protein B) [C17orf68]

==Publications==

{{medline-entry
|title=[[CTC1]]-[[STN1]] coordinates G- and C-strand synthesis to regulate telomere length.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29774655
|abstract=Coats plus ([[CP]]) is a rare autosomal recessive disorder caused by mutations in [[CTC1]], a component of the CST ([[CTC1]], [[STN1]], and TEN1) complex important for telomere length maintenance. The molecular basis of how [[CP]] mutations impact upon telomere length remains unclear. The [[CP]] [[CTC1]]  mutation has been previously shown to disrupt telomere maintenance. In this study, we used CRISPR/Cas9 to engineer this mutation into both alleles of HCT116 and [[RPE]] cells to demonstrate that [[CTC1]]:[[STN1]] interaction is required to repress telomerase activity. [[CTC1]]  interacts poorly with [[STN1]], leading to telomerase-mediated telomere elongation. Impaired interaction between [[CTC1]]  :[[STN1]] and DNA Pol-α results in increased telomerase recruitment to telomeres and further telomere elongation, revealing that C:S binding to DNA Pol-α is required to fully repress telomerase activity. [[CP]] [[CTC1]] mutants that fail to interact with DNA Pol-α resulted in loss of C-strand maintenance and catastrophic telomere shortening. Our findings place the CST complex as an important regulator of both G-strand extensions by telomerase and C-strand synthesis by DNA Pol-α.
|mesh-terms=* DNA Polymerase I
* DNA Replication
* HCT116 Cells
* HEK293 Cells
* Humans
* Telomere
* Telomere Homeostasis
* Telomere-Binding Proteins
|keywords=* DNA repair
* stem cell aging
* telomerase
* telomere
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052479
}}
{{medline-entry
|title=Stimulation of cell proliferation by glutathione monoethyl ester in aged bone marrow stromal cells is associated with the assistance of [[TERT]] gene expression and telomerase activity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27251157
|abstract=The proliferation and differentiation potential of aged bone marrow stromal cells (BMSCs) are significantly reduced. In order to improve the performance of the aged BMSCs, these cells were treated with 2 mM glutathione monoethyl ester (GSH-MEE) for 24 h. Proliferation rate, telomerase activity, telomere length, and differentiation to cholinergic neuron-like cells (CNLCs) were observed to increase. Though, the expression level of telomerase reverse transcriptase gene increased, but [[CTC1]] and [[TEN1]] genes from Ctc1-Stn1-Ten1 complex encoding proteins with regulatory function significantly decreased. Trypan blue exclusion assay was used to analyze the proliferation and, while telomere length, its several related gene expressions, and telomerase activity were measured using the real time reverse transcription-polymerase chain reaction and polymerase chain reaction enzyme-linked immunosorbent assay techniques, respectively. CNLCs differentiation potential was evaluated by estimating the percentage of choline acetyltransferase immunereactive cells.The results suggested that GSH-MEE could improve aged rat BMSC properties and would be of potential benefit for enhancing the performance of aged people's BMSCs. 
|mesh-terms=* Animals
* Bone Marrow Cells
* Cell Differentiation
* Cell Proliferation
* Choline O-Acetyltransferase
* Gene Expression Regulation, Developmental
* Glutathione
* Humans
* Mesenchymal Stem Cells
* Neurons
* Rats
* Telomerase
* Telomere
* Telomere-Binding Proteins
|keywords=* Aging
* Cholinergic neuron
* Glutathione
* Mesenchymal stromal cells
* Telomerase
* Telomere
|full-text-url=https://sci-hub.do/10.1007/s11626-016-0021-5
}}
{{medline-entry
|title=Genome wide association and linkage analyses identified three loci-4q25, 17q23.2, and 10q11.21-associated with variation in leukocyte telomere length: the Long Life Family Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24478790
|abstract=Leukocyte telomere length is believed to measure cellular aging in humans, and short leukocyte telomere length is associated with increased risks of late onset diseases, including cardiovascular disease, dementia, etc. Many studies have shown that leukocyte telomere length is a heritable trait, and several candidate genes have been identified, including [[TERT]], TERC, OBFC1, and [[CTC1]]. Unlike most studies that have focused on genetic causes of chronic diseases such as heart disease and diabetes in relation to leukocyte telomere length, the present study examined the genome to identify variants that may contribute to variation in leukocyte telomere length among families with exceptional longevity. From the genome wide association analysis in 4,289 LLFS participants, we identified a novel intergenic SNP rs7680468 located near [[PAPSS1]] and [[DKK2]] on 4q25 (p = 4.7E-8). From our linkage analysis, we identified two additional novel loci with HLOD scores exceeding three, including 4.77 for 17q23.2, and 4.36 for 10q11.21. These two loci harbor a number of novel candidate genes with SNPs, and our gene-wise association analysis identified multiple genes, including [[DCAF7]], [[POLG2]], [[CEP95]], and [[SMURF2]] at 17q23.2; and [[RASGEF1A]], [[HNRNPF]], ANF487, [[CSTF2T]], and [[PRKG1]] at 10q11.21. Among these genes, multiple SNPs were associated with leukocyte telomere length, but the strongest association was observed with one contiguous haplotype in [[CEP95]] and [[SMURF2]]. We also show that three previously reported genes-TERC, [[MYNN]], and OBFC1-were significantly associated with leukocyte telomere length at p empirical < 0.05. 

|keywords=* aging
* familial longevity
* family-based study
* genome wide association and linkage
* novel genes
* telomere length
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894567
}}
{{medline-entry
|title=Functional characterization of human [[CTC1]] mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease Coats plus.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23869908
|abstract=Coats plus is a rare recessive disorder characterized by intracranial calcifications, hematological abnormalities, and retinal vascular defects. This disease results from mutations in [[CTC1]], a member of the [[CTC1]]-[[STN1]]-[[TEN1]] (CST) complex critical for telomere replication. Telomeres are specialized DNA/protein structures essential for the maintenance of genome stability. Several patients with Coats plus display critically shortened telomeres, suggesting that telomere dysfunction plays an important role in disease pathogenesis. These patients inherit [[CTC1]] mutations in a compound heterozygous manner, with one allele encoding a frameshift mutant and the other a missense mutant. How these mutations impact upon telomere function is unknown. We report here the first biochemical characterization of human [[CTC1]] mutations. We found that all [[CTC1]] frameshift mutations generated truncated or unstable protein products, none of which were able to form a complex with [[STN1]]-[[TEN1]] on telomeres, resulting in progressive telomere shortening and formation of fused chromosomes. Missense mutations are able to form the CST complex at telomeres, but their expression levels are often repressed by the frameshift mutants. Our results also demonstrate for the first time that [[CTC1]] mutations promote telomere dysfunction by decreasing the stability of [[STN1]] to reduce its ability to interact with DNA Polα, thus highlighting a previously unknown mechanism to induce telomere dysfunction. 
|mesh-terms=* Animals
* Ataxia
* Brain Neoplasms
* Calcinosis
* Central Nervous System Cysts
* DNA Polymerase I
* Heterozygote
* Humans
* Leukoencephalopathies
* Mice
* Muscle Spasticity
* Mutant Proteins
* Mutation
* Protein Binding
* Retinal Diseases
* Seizures
* Telomere
* Telomere Homeostasis
* Telomere-Binding Proteins
|keywords=* aging
* mouse models
* telomeres
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083614
}}