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Objective: Telomeres are repetitive sequences localized at the ends of eukaryotic chromosomes comprising noncoding DNA and telomere-binding proteins. TRF1 and TRF2 both bind to the double-stranded telomeric DNA to regulate its length throughout the lifespan of eukaryotic cells. POT1 interacts with single-stranded telomeric DNA and contributes to protecting genomic integrity. Previous studies have shown that telomeres gradually shorten as ovaries age, coinciding with fertility loss. However, the molecular background of telomere shortening with ovarian aging is not fully understood. Methods: The present study aimed to determine the spatial and temporal expression levels of the TERT, TRF1, TRF2, and POT1 proteins in different groups of human ovaries: fetal (n = 11), early postnatal (n = 10), premenopausal (n = 12), and postmenopausal (n = 14). Also, the relative telomere signal intensity of each group was measured using the Q-FISH method. Results: We found that the telomere signal intensities decreased evenly and significantly from fetal to postmenopausal groups (P < 0.05). The TERT, TRF1, TRF2, and POT1 proteins were localized in the cytoplasmic and nuclear regions of the oocytes, granulosa and stromal cells. Furthermore, the expression levels of these proteins reduced significantly from fetal to postmenopausal groups (P < 0.05). Conclusion: These findings suggest that decreased TERT and telomere-binding protein expression may underlie the telomere shortening of ovaries with age, which may be associated with female fertility loss. Further investigations are required to elicit the molecular mechanisms regulating the gradual decrease in the expression of TERT and telomere-binding proteins in human oocytes and granulosa cells during ovarian aging. [ABSTRACT FROM AUTHOR]

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In principle, alterations in the telomere repeat sequence would be expected to disrupt the protective nucleoprotein complexes that confer stability to chromosome ends, and hence relatively rare events in evolution. Indeed, numerous organisms in diverse phyla share a canonical 6 bp telomere repeat unit (5'-TTAGGG-3'/5'-CCCTAA-3'), suggesting common descent from an ancestor that carries this particular repeat. All the more remarkable, then, are the extraordinarily divergent telomere sequences that populate the Saccharomycotina subphylum of budding yeast. These sequences are distinguished from the canonical telomere repeat in being long, occasionally degenerate, and frequently non-G/C-rich. Despite the divergent telomere repeat sequences, studies to date indicate that the same families of single-strand and double-strand telomere binding proteins (i.e., the Cdc13 and Rap1 families) are responsible for telomere protection in Saccharomycotina yeast. The recognition mechanisms of the protein family members therefore offer an informative paradigm for understanding the co-evolution of DNA-binding proteins and the cognate target sequences. Existing data suggest three potential, inter-related solutions to the DNA recognition problem: (i) duplication of the recognition protein and functional modification; (ii) combinatorial recognition of target site; and (iii) flexibility of the recognition surfaces of the DNA-binding proteins to adopt alternative conformations. Evidence in support of these solutions and the relevance of these solutions to other DNA-protein regulatory systems are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Shortening of telomere is associated with cellular senescence and cancer. This study aims to investigate the relationship between tumor grade and recurrence in relation to telomere length (TL), telomerase activity (TA) and telomere-binding proteins expression (TBPs) in patients with non-muscle invasive bladder cancer (NMIBC). Materials and Methods: Tumor/healthy tissues were collected from 58 patients (35 with and 23 without NMIBC). Cystoscopy was performed at 3, 6 and 12 months to determine recurrence. Tumor grades and recurrence were correlated with TL, TA and TBPs using the Kruskal-Wallis non-parametric test. Results were considered significant at P < 0.05. Results: Histological evaluation indicated 15 patients (42.9%) with high-grade (HG) and 20 patients (57.1%) with low-grade (LG) NMIBC. TL, TA and TBPs were found to be significantly different in tumors as compared with controls. A significant (p < 0.05) difference in the expression of TBPs was observed in the disease-free mucosa of cancer patients as compared with HG and LG tumors. In the follow-up, a total of 11 tumor recurrences were observed; among these eight recurrences were observed in patients with HG tumors and three in patients with LG tumors. TL, Human telomerase reverse transcriptase (hTERT) (that represents TA) and poly (ADP-ribose) polymerase 1 (PARP-1) in tumor samples and telomeric repeat binding factors TRF1, TRF2 and tankyrase (TANK) in normal mucosa obtained from the tumor group were respectively found to exhibit a positive and negative association with the risk of recurrence. Conclusions: Our study demonstrates that TL, TA and TBPs are altered in tumors and non-cancerous mucosa in patients with papillary urothelial NMIBC. Further studies are warranted to identify their suitability as a potential biomarker. [ABSTRACT FROM AUTHOR]

Aging phenotypes are dictated by myriad cellular changes including telomere shortening. In most tissues, telomere shortening is accelerated during replication if unrepaired oxidative damage to telomere sequences is present. However, the effect of reactive oxygen species exposure on skeletal muscle telomeres is unknown. We sought to determine if oxidative stress shortens telomeres in isolated adult rodent skeletal muscle fibers. Flexor digitorum brevis muscles were dissected from male mice (C57BL/6, long telomere and CAST/Ei, wild-derived, short telomere) and dissociated into single fibers. Fibers were cultured at an oxygen tension of 2%–5% for 5 days in control, hydrogen peroxide (oxidant), or a combination of N-acetylcysteine (antioxidant) and oxidant containing media. Telomere length, telomerase enzyme activity, and protein content of TRF1 and TRF2 were subsequently measured. In both strains, oxidative stress resulted in significant telomere shortening in isolated skeletal muscle fibers, likely by different mechanisms. Telomerase activity was not altered by oxidative stress treatment but was significantly different between strains, with greater telomerase activity in long-telomere–bearing C57BL/6 mice. These results provide important insights into mechanisms by which oxidative stress could shorten skeletal muscle telomeres. [ABSTRACT FROM PUBLISHER]

Telomeres are repetitive TG-rich DNA elements essential for maintaining the stability of genomes and replicative capacity of cells in almost all eukaryotes. Most of what is known about telomeres in plants comes from the angiosperm Arabidopsis thaliana, which has become an important comparative model for telomere biology. Arabidopsis tolerates numerous insults to its genome, many of which are catastrophic or lethal in other eukaryotic systems such as yeast and vertebrates. Despite the importance of Arabidopsis in establishing a model for the structure and regulation of plant telomeres, only a handful of studies have used this information to assay components of telomeres from across land plants, or even among the closest relatives of Arabidopsis in the plant family Brassicaceae. Here, we determined how well Arabidopsis represents Brassicaceae by comparing multiple aspects of telomere biology in species that represent major clades in the family tree. Specifically, we determined the telomeric repeat sequence, measured bulk telomere length, and analyzed variation in telomere length on syntenic chromosome arms. In addition, we used a phylogenetic approach to infer the evolutionary history of putative telomere-binding proteins, CTC1, STN1, TEN1 (CST), telomere repeat-binding factor like (TRFL), and single Myb histone (SMH). Our analyses revealed conservation of the telomeric DNA repeat sequence, but considerable variation in telomere length among the sampled species, even in comparisons of syntenic chromosome arms. We also found that the single-stranded and double-stranded telomeric DNA-binding complexes CST and TRFL, respectively, differ in their pattern of gene duplication and loss. The TRFL and SMH gene families have undergone numerous duplication events, and these duplicate copies are often retained in the genome. In contrast, CST components occur as single-copy genes in all sampled genomes, even in species that experienced recent whole genome duplication events. Taken together, our results place the Arabidopsis model in the context of other species in Brassicaceae, making the family the best characterized plant group in regard to telomere architecture. [ABSTRACT FROM AUTHOR]

Telomeres, noncoding hexameric tandem repeats located at the ends of chromosomes, maintain chromosome stability and genome integrity. These guanine-rich repeats are highly conserved during evolution, and their role is dependent on their length and structure. They have multiple functions, including regulating the reproductive lifespan by mediating synapsis and homologous recombination of the chromosomes. Short telomeres result in meiotic arrest, segregation abnormalities and dysjunction, which lead to an increased incidence of aneuploid germ cells. In addition, shortened telomeres in men result in apoptosis of germ cells, whereas, in women, they result in meiotic arrest. In somatic cells, telomere shortening occurs at each consecutive round of replication, which induces senescence in vitro and in vivo. However there is a 2-fold elongation of telomeres during spermatogenesis. Spermatozoa, are terminally differentiated cells, have longer telomeres than spermatogonia and pachytene spermatocytes. In addition to genetic factors, lifestyle factors and psychological stress also play crucial role in modulating telomere length. Because not much is known about its role in reproduction, we focused this review on the function, structure and length dynamics of the telomere in the reproductive process. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including telomere binding proteins (TeloBPs), vertebrate telomere repeat factor (TRF1), and cell evolution.

The nucleoprotein structures termed telomeres serve to prevent the mis-identification of eukaryotic chromosome ends as sites of DNA damage, but are also among the genomic regions that pose the most problems during DNA replication. Here, we summarize some of the apparent difficulties encountered by the DNA replication machinery when it approaches the chromosome ends. Eukaryotic cells have evolved diverse mechanisms to overcome these problems, underlining the importance of telomere maintenance for a number of aspects of chromosome function. Of particular interest in this respect are the ways in which telomere-binding proteins and components of the DNA damage response machinery may facilitate replication fork progression through telomeres. [ABSTRACT FROM AUTHOR]

Telomeres and their changes in length throughout the life span of cells have been intensively investigated in different organisms. Telomere length is assumed to control replicative senescence in mammalian cells. However, only very few data are available on the developmental dynamics of plant telomeres. Here, changes of telomere length and DNA-protein structure of Arabidopsis thaliana telomeres were analysed in different stages of development, with the main focus resting on the transition from pre-senescent to senescent leaves. The lengths of the telomeres, ranging from ca. 2.0 to 6.5 kb, do not significantly change during plant development indicating that telomere length is not involved in differentiation and replicative senescence nor in post-mitotic senescence of A. thaliana. In dedifferentiated cultured cells a slight increase in length can be determined. The nucleoprotein structure of the telomeric DNA was investigated by gel mobility shift assays, with synthetic oligonucleotides and nuclear protein extracts derived from four defined stages of post-mitotic leaf senescence. In all four stages, a highly salt-resistant DNA-protein complex was formed with the double-stranded as well as with the single-stranded G-rich telomeric DNA. An additional DNA-protein complex was identified in nuclear protein extracts isolated from plants in the transition stage from pre-senescence to senescence. The protein components of the DNA-protein complexes were analysed on native PAGE and SDS-PAGE gels. A protein of 67 kDa (ATBP1) bound to the telomeric DNA in all developmental stages. An additional protein of merely 22 kDa (ATBP2) was associated via protein-protein interaction with ATBP1 to form a higher-order complex exclusively during the onset of senescence. DNA interaction of this higher-order protein complex seems to be restricted to double-stranded telomeric DNA. The defined period of ATBP1/ATBP2 complex formation with the telomeric DNA probably indicates that ATBP2 is involved in the onset of post-mitotic leaf senescence by either disturbing an established or establishing an additional function exhibited by the telomeres in the interphase nuclei. [ABSTRACT FROM AUTHOR]

The nucleoprotein structure of Arabidopsis thaliana telomeres was investigated. A protein specifically binding to telomeric sequences was characterized by gel mobility shift assays with synthetic oligonucleotides consisting of four 7 bp telomeric repeats of Arabidopsis (TTTAGGG) and crude nuclear protein extracts of Arabidopsis leaves. These DNA-protein binding studies revealed that the binding affinity of this telomere-binding protein to the G-rich single-strand as well as to the double-stranded telomeric DNA is much higher than to the C-rich single-strand. The molecular mass of the protein was identified by SDS-PAGE to be 67 kDa. The isoelectric points were determined to be 5.0, 4.85 and 4.7, respectively, indicating that either one protein with different modifications or three slightly different proteins have been isolated. An RNA component, possibly serving as a template for reverse transcription of a plant telomerase, does not mediate the DNA-protein contact because the DNA-protein interactions were not RNAse-sensitive. [ABSTRACT FROM AUTHOR]