Genomes and Genes
Summary: Maintenance of TELOMERE length. During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING.) Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends.
- Koh C, Khattar E, Leow S, Liu C, Müller J, Ang W, et al. Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity. J Clin Invest. 2015;125:2109-22 pubmed publisher..Based on these data, we conclude that reactivation of TERT, a direct transcriptional MYC target in tumors, provides a feed-forward mechanism to potentiate MYC-dependent oncogenesis. ..
- Haycock P, Burgess S, Nounu A, Zheng J, Okoli G, Bowden J, et al. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. JAMA Oncol. 2017;3:636-651 pubmed publisher..28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases. ..
- Marcon F, Siniscalchi E, Andreoli C, Allione A, Fiorito G, Medda E, et al. Telomerase activity, telomere length and hTERT DNA methylation in peripheral blood mononuclear cells from monozygotic twins with discordant smoking habits. Environ Mol Mutagen. 2017;58:551-559 pubmed publisher..Environ. Mol. Mutagen. 58:551-559, 2017. © 2017 Wiley Periodicals, Inc. ..
- McKay J, Hung R, Han Y, Zong X, Carreras Torres R, Christiani D, et al. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes. Nat Genet. 2017;49:1126-1132 pubmed publisher..Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer...
- Suzuki A, Matsumoto Y, Enokido M, Shirata T, Goto K, Otani K. Relationship between interpersonal sensitivity and leukocyte telomere length. BMC Med Genet. 2017;18:112 pubmed publisher..044) associated with shorter telomere length. The present study suggests that subjects with higher interpersonal sensitivity have shorter leukocyte telomere length, implying that interpersonal sensitivity has an impact on cellular aging. ..
- Vazirpanah N, Verhagen F, Rothova A, Missotten T, van Velthoven M, den Hollander A, et al. Aberrant leukocyte telomere length in Birdshot Uveitis. PLoS ONE. 2017;12:e0176175 pubmed publisher..These findings suggest that BU is accompanied by significantly longer LTL. ..
- Wu Z, Liu J, Zhang Q, Lv D, Wu N, Zhou J. Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection. Nucleic Acids Res. 2017;45:3308-3322 pubmed publisher..This study provides a mechanistic link between histone H2B ubiquitination and telomere replication. ..
- Cheng Y, Kao T, Chang Y, Wu C, Peng T, Wu L, et al. Examining the gender difference in the association between metabolic syndrome and the mean leukocyte telomere length. PLoS ONE. 2017;12:e0180687 pubmed publisher..05) in both males and females. In summary, our study indicated that an increment of MetS component is strongly associated with shorter LTL, especially in the female population. ..
- Adam R, Díez González L, Ocana A, Seruga B, Amir E, Templeton A. Prognostic role of telomere length in malignancies: A meta-analysis and meta-regression. Exp Mol Pathol. 2017;102:455-474 pubmed publisher..Standardization of measurement and reporting of TL is warranted before the prognostic value of TL can be accurately assessed. ..
- Khan S, Singer B, Vaughan D. Molecular and physiological manifestations and measurement of aging in humans. Aging Cell. 2017;16:624-633 pubmed publisher..This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging...
- Nezu T, Hosomi N, Takahashi T, Anno K, Aoki S, Shimamoto A, et al. Telomere G-tail Length is a Promising Biomarker Related to White Matter Lesions and Endothelial Dysfunction in Patients With Cardiovascular Risk: A Cross-sectional Study. EBioMedicine. 2015;2:960-7 pubmed publisher..Telomere G-tail length is associated with age and vascular risk factors, and might be superior to total telomere length as a marker of endothelial dysfunction and ARWMC severity. ..
- Tummala H, Walne A, Collopy L, Cardoso S, de la Fuente J, Lawson S, et al. Poly(A)-specific ribonuclease deficiency impacts telomere biology and causes dyskeratosis congenita. J Clin Invest. 2015;125:2151-60 pubmed publisher..Collectively, these results identify a role for PARN in telomere maintenance and demonstrate that it is a disease-causing gene in a subset of patients with severe DC. ..
- Smekalova E, Malyavko A, Zvereva M, Mardanov A, Ravin N, Skryabin K, et al. Specific features of telomerase RNA from Hansenula polymorpha. RNA. 2013;19:1563-74 pubmed publisher..Mutational analysis of HpTER confirmed that the incorporation of dT functions to limit telomere length in this species. ..
- Wang Y, SHARPLESS N, Chang S. p16(INK4a) protects against dysfunctional telomere-induced ATR-dependent DNA damage responses. J Clin Invest. 2013;123:4489-501 pubmed publisher..Our results provide experimental evidence that p16(INK4a) exerts protective functions in proliferative cells bearing dysfunctional telomeres. ..
- Williams D, Palaniswamy S, Sebert S, Buxton J, Blakemore A, Hypponen E, et al. 25-Hydroxyvitamin D Concentration and Leukocyte Telomere Length in Young Adults: Findings From the Northern Finland Birth Cohort 1966. Am J Epidemiol. 2016;183:191-8 pubmed publisher..3%, 95% confidence interval -0.6, -0.1). These findings suggest that vitamin D status is unlikely to be an important determinant of LTL, at least by young adulthood. Inflammation may partly mediate associations of adiposity with LTL. ..
- Cesena D, Cassani C, Rizzo E, Lisby M, Bonetti D, Longhese M. Regulation of telomere metabolism by the RNA processing protein Xrn1. Nucleic Acids Res. 2017;45:3860-3874 pubmed publisher..These findings reveal novel roles for RNA processing proteins in the regulation of telomere metabolism with implications for genome stability in eukaryotes. ..
- Ventura Ferreira M, Crysandt M, Ziegler P, Hummel S, Wilop S, Kirschner M, et al. Evidence for a pre-existing telomere deficit in non-clonal hematopoietic stem cells in patients with acute myeloid leukemia. Ann Hematol. 2017;96:1457-1461 pubmed publisher..Our data indicate a pre-existing telomere deficit in non-clonal hematopoiesis of AML patients providing a link between age and AML development. ..
- Williams D, Buxton J, Kantomaa M, Tammelin T, Blakemore A, Jarvelin M. Associations of Leukocyte Telomere Length With Aerobic and Muscular Fitness in Young Adults. Am J Epidemiol. 2017;185:529-537 pubmed publisher..LTL may relate to aspects of physical fitness in young adulthood, but replication of these findings is required, along with further studies to help assess directions and causality in these associations. ..
- Jin K, Xiang Y, Tang J, Wu G, Li J, Xiao H, et al. miR-34 is associated with poor prognosis of patients with gallbladder cancer through regulating telomere length in tumor stem cells. Tumour Biol. 2014;35:1503-10 pubmed..Both low miR-34a expression and long telomere length are markers for poor prognosis of patients with gallbladder adenocarcinoma. Our study also suggests that the miR-34a gene could be a target for targeting therapy of GBC. ..
- Dean S, Zhang C, Gao J, Roy S, Shinkle J, Sabarinathan M, et al. The association between telomere length and mortality in Bangladesh. Aging (Albany NY). 2017;9:1537-1551 pubmed publisher..03 and P=0.04). Results from pooled analyses of all cohorts were consistent with HEALS and BEST. This is the first study demonstrating an association between short TL and increased mortality in a population of non-European ancestry. ..
- Kosova A, Khodyreva S, Lavrik O. Role of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) in DNA Repair. Biochemistry (Mosc). 2017;82:643-654 pubmed publisher..Moreover, GAPDH can interact with proteins participating in DNA repair, such as APE1, PARP1, HMGB1, and HMGB2. In this review, the functions of GAPDH associated with DNA repair are discussed in detail. ..
- Zhan Y, Karlsson I, Karlsson R, Tillander A, Reynolds C, Pedersen N, et al. Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study. Circ Res. 2017;121:214-219 pubmed publisher..86; 95% confidence interval, 1.01-3.41; P=0.04). Overall, our findings support a role of insulin as a mediator on the causal pathway from shorter telomeres to CHD pathogenesis. ..
- Park H, Park S, Im K, Kim S, Kim J, Hwang S, et al. Telomere length and somatic mutations in correlation with response to immunosuppressive treatment in aplastic anaemia. Br J Haematol. 2017;178:603-615 pubmed publisher..In conclusion, the patients with clonal changes or TL attrition showed a poor response to IST. Shorter TL can be used not only as a biomarker, but also as a predictive marker for treatment response to IST. ..
- Charif N, Li Y, Targa L, Zhang L, Ye J, Li Y, et al. Aging of bone marrow mesenchymal stromal/stem cells: Implications on autologous regenerative medicine. Biomed Mater Eng. 2017;28:S57-S63 pubmed publisher..It will lead to in vitro cell aging that could modify cell properties. This review recapitulates several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties. ..
- Khoueiry R, Sohni A, Thienpont B, Luo X, Velde J, Bartoccetti M, et al. Lineage-specific functions of TET1 in the postimplantation mouse embryo. Nat Genet. 2017;49:1061-1072 pubmed publisher..Collectively, our study highlights an interplay between the catalytic and non-catalytic activities of TET1 that is essential for normal development. ..
- Endicott A, Taylor J, Walsh K. Telomere length connects melanoma and glioma predispositions. Aging (Albany NY). 2016;8:423-4 pubmed
- Mason P, Bessler M. mRNA deadenylation and telomere disease. J Clin Invest. 2015;125:1796-8 pubmed publisher..Together, the results of this study support PARN as a DC-associated gene and suggest a potential link between p53 and telomere shortening. ..
- Østhus I, Lydersen S, Dalen H, Nauman J, Wisløff U. Association of Telomere Length With Myocardial Infarction: A Prospective Cohort From the Population Based HUNT 2 Study. Prog Cardiovasc Dis. 2017;59:649-655 pubmed publisher..Future large scale prospective studies are needed to confirm these findings and explore the potential association between TL and MI. ..
- MartÃnez P, Blasco M. Telomere-driven diseases and telomere-targeting therapies. J Cell Biol. 2017;216:875-887 pubmed publisher..Here we review the molecular mechanisms underlying telomere-driven diseases and highlight recent advances in the preclinical development of telomere-targeted therapies using mouse models. ..
- Wang S, Pike A, Lee S, Strong M, Connelly C, Greider C. BRD4 inhibitors block telomere elongation. Nucleic Acids Res. 2017;45:8403-8410 pubmed publisher..Telomerase enzymatic activity was not directly affected by BRD4 inhibition. BRD4 is in clinical trials for a number of cancers, but its effects on telomere maintenance have not been previously investigated. ..
- Kupiec M. Biology of telomeres: lessons from budding yeast. FEMS Microbiol Rev. 2014;38:144-71 pubmed
- Zheng X, Nie X, Fang Y, Zhang Z, Xiao Y, Mao Z, et al. A Cisplatin Derivative Tetra-Pt(bpy) as an Oncotherapeutic Agent for Targeting ALT Cancer. J Natl Cancer Inst. 2017;109: pubmed publisher..These results reveal the potential of Tetra-Pt(bpy) as a novel oncotherapeutic agent for targeting ALT cancer cells. ..
- Dagnall C, Hicks B, Teshome K, Hutchinson A, Gadalla S, Khincha P, et al. Effect of pre-analytic variables on the reproducibility of qPCR relative telomere length measurement. PLoS ONE. 2017;12:e0184098 pubmed publisher..This study illustrates the importance of uniform sample handling, from DNA extraction through data generation and analysis, in using qPCR to determine RTL. ..
- Sobinoff A, Allen J, Neumann A, Yang S, Walsh M, Henson J, et al. BLM and SLX4 play opposing roles in recombination-dependent replication at human telomeres. EMBO J. 2017;36:2907-2919 pubmed publisher..Our data are consistent with ALT being a conservative DNA replication process, analogous to break-induced replication, which is dependent on BTR and counteracted by SLX4 complex-mediated resolution events. ..
- Braun D, Rao J, Mollet G, Schapiro D, Daugeron M, Tan W, et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet. 2017;49:1529-1538 pubmed publisher..We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. ..
- Tummala H, Walne A. Long tails, short telomeres: Dyskeratosis congenita. Oncotarget. 2015;6:13856-7 pubmed
- Lee D, Kim E, Neblett E. The link between discrimination and telomere length in African American adults. Health Psychol. 2017;36:458-467 pubmed publisher..This finding helps advance our understanding of how discrimination generates greater disease vulnerability and premature death in African Americans. (PsycINFO Database Record ..
- Polonis K, Somers V, Becari C, Covassin N, Schulte P, Druliner B, et al. Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening. Am J Physiol Heart Circ Physiol. 2017;313:H1022-H1030 pubmed publisher..A better understanding of the mechanisms underlying telomere dynamics may identify targets for therapeutic intervention in cardiovascular aging/other chronic diseases. ..
- Runov A, Vonsky M, Mikhelson V. [DNA methylation level and telomere length as a basis for the biological aging clock model construction]. Tsitologiia. 2015;57:192-6 pubmed..Application of qPCR to determina the length of telomeres and MS-HRM for analysis of DNA methylation will help us to determine the parameters of interest quickly when using a minimum set of equipment. ..
- Thomay K, Fedder C, Hofmann W, Kreipe H, Stadler M, Titgemeyer J, et al. Telomere shortening, TP53 mutations and deletions in chronic lymphocytic leukemia result in increased chromosomal instability and breakpoint clustering in heterochromatic regions. Ann Hematol. 2017;96:1493-1500 pubmed publisher..We conclude that telomere shortening in combination with loss of TP53 induces increased chromosomal instability with preferential involvement of (near-) heterochromatic regions. ..
- Wagner K, Ying Y, Leong W, Jiang J, Hu X, Chen Y, et al. The differential spatiotemporal expression pattern of shelterin genes throughout lifespan. Aging (Albany NY). 2017;9:1219-1232 pubmed publisher..Together, this work shows that the shelterin subunits exhibit distinct spatiotemporal expression patterns, suggesting important tissue-specific functions during development and aging. ..