12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Replicative capacity of a cell is strongly correlated with telomere length regulation. Aberrant lengthening or reduction in the length of telomeres can lead to health anomalies, such as cancer or premature aging. Telomerase is a master regulator for maintaining replicative potential in most eukaryotic cells. It does so by controlling telomere length at chromosome ends. Akin to cancer cells, most single-cell eukaryotic pathogens are highly proliferative and require persistent telomerase activity to maintain constant length of telomere and propagation within their host. Although telomerase is key to unlimited cellular proliferation in both cases, not much was known about the role of telomerase in human parasites (malaria, Trypanosoma, etc.) until recently. Since telomerase regulation is mediated via its own structural components, interactions with catalytic reverse transcriptase and several factors that can recruit and assemble telomerase to telomeres in a cell cycle-dependent manner, we compare and discuss here recent findings in telomerase biology in cancer, aging and parasitic diseases to give a broader perspective of telomerase function in human diseases.

          Related collections

          Most cited references179

          • Record: found
          • Abstract: found
          • Article: not found

          The genome of the African trypanosome Trypanosoma brucei.

          African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            How telomeres solve the end-protection problem.

            The ends of eukaryotic chromosomes have the potential to be mistaken for damaged or broken DNA and must therefore be protected from cellular DNA damage response pathways. Otherwise, cells might permanently arrest in the cell cycle, and attempts to "repair" the chromosome ends would have devastating consequences for genome integrity. This end-protection problem is solved by protein-DNA complexes called telomeres. Studies of mammalian cells have recently uncovered the mechanism by which telomeres disguise the chromosome ends. Comparison to unicellular eukaryotes reveals key differences in the DNA damage response systems that inadvertently threaten chromosome ends. Telomeres appear to be tailored to these variations, explaining their variable structure and composition.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines.

              The gradual loss of DNA from the ends of telomeres has been implicated in the control of cellular proliferative potential. Telomerase is an enzyme that restores telomeric DNA sequences, and expression of its activity was thought to be essential for the immortalization of human cells, both in vitro and in tumor progression in vivo. Telomerase activity has been detected in 50-100% of tumors of different types, but not in most normal adult somatic tissues. It has also been detected in about 70% of human cell lines immortalized in vitro and in all tumor-derived cell lines examined to date. It has previously been shown that in vitro immortalized telomerase-negative cell lines acquire very long and heterogeneous telomeres in association with immortalization presumably via one or more novel telomere-lengthening mechanisms that we refer to as ALT (alternative lengthening of telomeres). Here we report evidence for the presence of ALT in a subset of tumor-derived cell lines and tumors. The maintenance of telomeres by a mechanism other than telomerase, even in a minority of cancers, has major implications for therapeutic uses of telomerase inhibitors.
                Bookmark

                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                24 January 2018
                February 2018
                : 19
                : 2
                : 333
                Affiliations
                Department of Biological Sciences, The University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223, USA; adey2@ 123456uncc.edu
                Author notes
                [* ]Correspondence: k.chakrabarti@ 123456uncc.edu ; Tel.: +1-704-687-1882
                Article
                ijms-19-00333
                10.3390/ijms19020333
                5855555
                29364142
                bbcdc6b0-ffd4-4a76-863e-3a73d1b12d2f
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 December 2017
                : 17 January 2018
                Categories
                Review

                Molecular biology
                telomerase,telomere,ter,tert,parasite,trypanosoma brucei,plasmodium falciparum,rna,rnp,dna repair,cellular senescence,cancer,ageing

                Comments

                Comment on this article