The POT1-TPP1 telomere complex is a telomerase processivity factor.

Department of Biological Chemistry, University of Michigan Medical School, MSRBIII 5301D, 1150 W. Medical Center Drive, Ann Arbor, Michigan 48109, USA.
Nature (Impact Factor: 42.35). 03/2007; 445(7127):506-10. DOI: 10.1038/nature05454
Source: PubMed

ABSTRACT Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 (protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1-TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.

Download full-text


Available from: Yuting Yang, Jul 02, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Telomere plays key roles in maintaining chromosome stability and cell replicative capacity. Telomere shortening occur concomitant with aging. Abnormal short telomere associated with some diseases, such as dyskeratosis congenita, idiopathic pulmonary fibrosis and aplastic anemia. Telomere is longer in pluripotent stem cells than in somatic cells. During preimplantation development, the telomeres lengthen significantly. Furthermore, during somatic cell reprogramming, telomere elongation is of great importance in the acquisition of authentic pluripotency. This review focuses primarily on regulatory mechanisms of telomere length, telomere length maintenance in pluripotent cells, telomere length extension in early embryo development, and also on telomere rejuvenation in somatic cell reprogramming. Telomere related diseases were also touched in this review. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 10/2014; 229(10). DOI:10.1002/jcp.24537 · 3.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The ends of chromosoms, telomeres are bound with a number of proteins which protect and stabilize telomeres against degredation, end to end fusion and aberrant recombinations. Telomeric DNA is bound of two groups of proteins, which are double-stranded telomeric DNA bindings proteins, and single stranded telomeric binding proteins. Among telomere binding proteins, protections of telomere 1 protein is a single stranded telomere binding proteins and suggested to be a significant player for telomere elongation and has an association with an enzyme called as telomerase which is an intrinsic reverse transcriptase. Telomerase synthesizes hexameric telomeric repeats onto the chromosomes thereby compansating telomere loss in immortal cells, such as tumor cells, whereas telomeres are shorthened with each division in normal cells. PCR-based TRAP (telomeric repeat amplification protocol) assay is a very sensitive assay for the detection of enzymatic activity of telomerase even if a few numbers of cancerous cells are available. The association between telomerase activity and hPOT1 expression in colorectal cancer is still unclear. Protein extraction was performed from specimens of matched normal and colorectal cancer specimens. Protein concentrations were determined by Bradford assay. Optimized protein concentrations were used for TRAP Assay. TRAP products were seperated by vertical gel electrophoresis on 12.5% polyacrylamide gels and visualized by silver staining. Gene expression of hPOT1 was determined by qPCR analysis. The results demonstrated that all tumor tissues were telomerase positive whereas all corresponding normal tissue was telomerase negative. Among clinicopathological findings, telomerase activity was found to be associated with stage, histology, localization, distant metastasis and lymph node metastasis of tumor in the current study. Although all of the clinicopathological findings differed in the expression of hPOT1 compared to normal tissues, they did not differ from each other significantly, except side of tumor and lymph node metastasis. Telomerase activity and hPOT1 gene expression may serve as a promising tumor marker for colorectal cancer and there is a close association between the enzymatic activty of telomerase and the expression of human protection of telomere 1 gene.
    Biomedecine [?] Pharmacotherapy 09/2014; DOI:10.1016/j.biopha.2014.08.014 · 2.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Chromosome Research 05/2014; 22(2). DOI:10.1007/s10577-014-9423-y · 2.69 Impact Factor