The telosome/shelterin complex and its functions. Genome Bio 9:232

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Baylor Plaza, Houston, TX 77030, USA.
Genome biology (Impact Factor: 10.81). 10/2008; 9(9):232. DOI: 10.1186/gb-2008-9-9-232
Source: PubMed


The telomeres that cap the ends of eukaryotic chromosomes serve a dual role in protecting the chromosome ends and in intracellular signaling for regulating cell proliferation. A complex of six telomere-associated proteins has been identified--the telosome or shelterin complex--that is crucial for both the maintenance of telomere structure and its signaling functions.

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    • "Given the population specificity of genetic variants associated with telomeres previously analyzed, we replicated significant results in a northern Italian population, in order to evaluate whether our results could be generalized. In particular, we analyzed, together with the TERC and TERT, some of the genes which are not directly involved in telomere elongation but are essential for telomere stability and structure (Kaminker et al. 2001; Xin et al. 2008). Among these, TEP1 specifically interacts with the telomerase RNA; TERF1, TERF2 and TERF2IP are located in the shelterin-complex that protects the telomeres from degradation and inappropriate DNA repair, prevents end-to-end fusion, atypical recombination, and premature senescence; TNKS and TNKS2 are other important telomere-associated proteins associated with telomeric DNA. "
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    ABSTRACT: Leukocyte telomere length (LTL) has been observed to be hereditable and correlated with longevity. However, contrasting results have been reported in different populations on the value of LTL heritability and on how biology of telomeres influences longevity. We investigated whether the variability of genes correlated to telomere maintenance is associated with telomere length and affects longevity in a population from Southern Italy (20-106 years). For this purpose we analyzed thirty-one polymorphisms in eight telomerase-associated genes of which twelve in the genes coding for the core enzyme (TERT and TERC) and the remaining in genes coding for components of the telomerase complex (TERF1, TERF2, TERF2IP, TNKS, TNKS2 and TEP1). We did not observe (after correcting for multiple testing) statistically significant associations between SNPs and LTL, possibly suggesting a low genetic influence of the variability of these genes on LTL in the elderly. On the other hand, we found that the variability of genes encoding for TERF1 and TNKS2, not directly involved in LTL, but important for keeping the integrity of the structure, shows a significant association with longevity. This suggests that the maintenance of these chromosomal structures may be critically important for preventing, or delaying, senescence and aging. Such a correlation was not observed in a population from northern Italy that we used as an independent replication set. This discrepancy is in line with previous reports regarding both the population specificity of results on telomere biology and the differences of aging in northern and southern Italy.
    Biogerontology 01/2015; 16(3). DOI:10.1007/s10522-015-9551-6 · 3.29 Impact Factor
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    • "Other mediators of cellular senescence include TRF (telomeric repeat binding factor), XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5), and SIRT1 (sirtuin 1). TRF1 and TRF2 are telomeric proteins that function to form and maintain telomere structure [123, 124]. XRCC5 is involved in repairing DNA double-strand breaks [125]. "
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    ABSTRACT: Osteoarthritis (OA) is closely associated with aging, but its underlying mechanism is unclear. Recent publications were reviewed to elucidate the connection between aging and OA. With increasing OA incidence, more senior people are facing heavy financial and social burdens. Age-related OA pathogenesis is not well understood. Recently, it has been realized that age-related changes in other tissues besides articular cartilage may also contribute to OA development. Many factors including senescence-related secretory phenotypes, chondrocytes' low reactivity to growth factors, mitochondrial dysfunction and oxidative stress, and abnormal accumulation of advanced glycation end products (AGEs) may all play key roles in the pathogenesis of age-related OA. Lately, epigenetic regulation of gene expression was recognized for its impact on age-related OA pathogenesis. Up to now, few studies have been reported about the role of miRNA and long-noncoding RNA (lncRNA) in age-related OA. Research focusing on this area may provide valuable insights into OA pathogenesis. OA-induced financial and social burdens have become an increasingly severe threat to older population. Age-related changes in noncartilage tissue should be incorporated in the understanding of OA development. Growing attention on oxidative stress and epigenetics will provide more important clues for the better understanding of the age-related OA.
    07/2013; 2013(1):916530. DOI:10.1155/2013/916530
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    • "Chromosomal ends or telomeres are specialized protein–DNA complexes that ensure chromosome stability and integrity (Palm & de Lange, 2008; Xin et al., 2008; O'Sullivan & Karlseder, 2010). In mammalian cells, the six-protein telosome/shelterin complex (TRF1, TRF2, RAP1, TIN2, TPP1, and POT1) assembles on telomeres and recruits the telomerase as well as other factors from diverse pathways (e.g., DNA damage response) for telomere maintenance and protection (de Lange, 2005; O'Connor et al., 2006; Nandakumar & Cech, 2013). "
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    ABSTRACT: Telomeres are specialized structures at the ends of eukaryotic chromosomes that are important for maintaining genome stability and integrity. Telomere dysfunction has been linked to aging and cancer development. In mammalian cells, extensive studies have been carried out to illustrate how core telomeric proteins assemble on telomeres to recruit the telomerase and additional factors for telomere maintenance and protection. In comparison, how changes in growth signaling pathways impact telomeres and telomere-binding proteins remains largely unexplored. The phosphatidylinositol 3-kinase (PI3-K)/Akt (also known as PKB) pathway, one of the best characterized growth signaling cascades, regulates a variety of cellular function including cell proliferation, survival, metabolism, and DNA repair, and dysregulation of PI3-K/Akt signaling has been linked to aging and diseases such as cancer and diabetes. In this study, we provide evidence that the Akt signaling pathway plays an important role in telomere protection. Akt inhibition either by chemical inhibitors or small interfering RNAs induced telomere dysfunction. Furthermore, we found that TPP1 could homodimerize through its OB fold, a process that was dependent on the Akt kinase. Telomere damage and reduced TPP1 dimerization as a result of Akt inhibition was also accompanied by diminished recruitment of TPP1 and POT1 to the telomeres. Our findings highlight a previously unknown link between Akt signaling and telomere protection. This article is protected by copyright. All rights reserved.
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