The Discovery Telomerase Essay

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The Discovery Telomerase

The linear chromosomes of eukaryotes are more complex than the circular chromosomes of the bacteria. Due to the biochemical properties of DNA polymerases, the replication of the eukaryotic chromosomes poses a special problem: the maintenance of the length of the linear chromosomes. However, it was discovered that a unique enzyme complex appears to play a crucial in maintaining the length of eukaryotic chromosomes. This enzyme is known as the telomerase. Its regulative action on the eukaryotic cell implies that it may also be involved in the process of aging and in the development of cancer cells.

In this paper, the telomerase becomes the focus of study. The discovery, properties, and functions of the telomerase inside the eukaryotic cells will be described, based on the recent scientific studies that have been conducted about them. And finally, current and potential applications that involve this enzyme, in the field of biotechnology, will be presented. The Discovery of Telomerase When the telomerase was first discovered by Carol Greider in 1984, many geneticists and molecular biologists like her have already been puzzling over the observation that the tips of chromosomes are stabilised by telomeres.

Telomeres are mere regions in the DNA in which sections of them are no longer copied during the process of cell division and chromosome replication (Vermolen 2005). But the fact that a small section of a telomere is not copied should result in shorter telomeres in the daughter cells. Strangely, this does not occur and scientists can only surmise that something maintains the length of the telomere and it could be an enzyme that is yet unknown. Then, on that fateful Christmas Day in 1984, Greider found the elusive enzyme through the use of autoradiography (Skloot 2001).

The telomerase is the enzyme that is responsible for maintaining the genetic material found at the tips of the chromosomes. The Properties of Telomerase The telomerase is an enzyme and this brings to mind two basic characteristics. First, any enzyme is composed of a protein. In the case of telomerase, the protein is the RNA and it can be considered as a ribozyme (Brown 2005). And second, any enzyme is a natural catalyst of all chemical reactions within the body of an organism. This means that the telomerase facilitates a vital biochemical reaction.

But the exact mechanism that the telomerase executes to maintain the length of the telomere during chromosomal replication can only be determined if the properties of it are known. And the properties can be known if the specific nature of the structure of the RNA is established. The telomerase is composed of two components, the essential RNA and the TERT. The latter, which stands for telomerase reverse transcriptase, is the catalytic protein. It “contains sequence motifs homologous to those in the catalytic domain of reverse transcriptase enzymes” (Chen & Greider 2004, p.

14683). This is concluded because the TERT is remains the same in all eukaryotes. The structure of the RNA component, however, is more challenging to characterise. This is because the telomerase RNA varies in terms of size and sequence. Fortunately, the overall structure of the telomerase RNA in many ciliates and vertebrates was eventually established (Chen, Blasco & Greider 2000). The common process utilized was the phylogenetic analysis (Tzfati 2003). However, the characterization of telomerase RNA did not reveal similarities.

There are large differences among the telomerase RNA structures of different organisms. For example, the RNA of ciliates has a conserved sequence motif found in helix I (Lai 2002), where as the RNA of yeasts seeks several helical regions as the binding sites for the telomerase’s Est1 protein (Peterson et al 2001). Thus, there was a need to ascertain a core structure. This core structure is also referred to as the secondary Blackburn (2004) and her colleagues, by using telomerase RNAs of yeasts, proposed a core structure out of the process of delineating nucleotides and base pairings.

They showed that a pseudoknot structure is an essential component of the telomerase RNA because it plays an important role during the binding process. Figure 1: The TERT binding and the pseudoknot The Functions of Telomerase The most obvious function of the telomerase, as stated before, is the maintenance of the length of the linear chromosomes of eukaryotes. This is carried out through a process known as reverse transcription. But, among scientists, this general statement is insufficient, especially before the advancing knowledge in biochemistry.

And now that the structure of the telomerase is established, the next question to be answered is how the telomerase actually and specifically works. There is no consensus so far, but the results of various studies can be combined to form a better picture of the function of telomerase. Here are three of the most significant ones. First, it was firmly established by several studies that there is a long-range base-pairing that occurs at the Est2 binding site (Chappell & Lundblad 2004; Dandjinou et al 2004; Lin et al 2004; Zapulla & Cech 2004).

Second, the pseudoknot performs various functions: binding at Est2 among yeasts and other replication-related activities among vertebrates (Livengood et al 2002). And third, the TERT proteins of the telomerase locate specific domains and these domains are referred to as motif T. This motif T is vital for RNA binding (Friedman & Cech 1999; Kelleher et al 2002). The specific actions of the two components of the telomerase are vital towards the determining its applications. Current and Potential Applications of Telomerase

There have been several misunderstandings about the application of telomerase in the field of biotechnology. The most popular false notion about telomerase is that it is the fountain of youth. Telomerase does not make a person stay young forever. What the telomerase can do is to support the replication of the chromosome and then, after many years, allow the state of senescence. It must be remembered that the telomerase only act upon the tips of the chromosomes and not on the lifestyle of a person.

This implies that if a person decides to live a dangerous or unhealthy lifestyle, neither his telomerase nor any modification on this enzyme will ever prevent his early death. The telomerase does not immortalize any organism. But this does not mean that the telomerase has no significant application. One of the most significant applications of telomerase is in the field of oncology. That is, the telomerase has been found to act abnormally during the replication of cancer cells. In normal cells, the action of telomerase ceases right after the chromosomal replication.

But in cancer cells, the telomerase remains active. Scientists assume that there must be some structural difference between the telomerase of normal cells and that of cancer cells. If the structural difference is found, it might be possible for molecular biologists to seek out cancerous cells by seeking the telomerase only. Then, a person who has cancer at the early stages can be diagnosed immediately and can utilize cancer therapeutic treatments that involve the inhibition of the abnormal telomerase (Shay et al 2001). Conclusion

The discovery of the telomerase is one of the most significant events in science history. It can be considered as vital as the discovery of the double helix structure of the DNA. This is because this enzyme allows the accurate and regulated replication of the linear chromosomes of eukaryotes. But, just as the discovery of the enzyme was challenging, the establishment of its properties and functions are equally difficult to carry out. Yet, molecular biologists persevere and came up with interesting possible applications of telomerase. Bibliography

Blackburn, EH, Lin, J, Ly, H, Hussain, A, Abraham, M, Pearl, S, Tzfati, Y, Parslow, TG 2004, ‘A universal telomerase RNA core structure includes structured motifs required for binding the telomerase reverse transcriptase protein’ Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 41, October, pp. 14713-14718, National Academy of Sciences pnas. 0405879101 viewed 10 September 2007, http://www. pnas. org/cgi/content/abstract/101/41/14713. Brown, J 2005, ‘What the Heck is an Enzyme’ Bugs in the News, viewed 10 September 2007, http://people. ku. edu/~jbrown/whatheck.

html. Chappell, AS, Lundblad, V 2004, ‘Structural Elements Required for Association of the Saccharomyces cerevisiae Telomerase RNA with the Est2 Reverse Transcriptase’ Molecular Cell Biology, 24: 7720-7736. Chen, JL, Blasco, MA, Greider, CW 2000, ‘Secondary structure of vertebrate telomerase RNA’ Cell, 100: 503-514. Chen, JL, Greider, CW 2004, ‘An emerging consensus for telomerase RNA structure’ Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 41, October, pp. 14683-14684, National Academy of Sciences pnas. 0406204101 viewed 10 September 2007, http://www.

pnas. org/cgi/content/full/101/41/14683. Dandjinou, At, Levesque, N, Larose, S, Lucier, JF, Abou-Elela, S, Wellinger RJ 2004, ‘A phylogenetically based secondary structure for the yeast telomerase RNA’ Current Biology, 14: 1148-1158. Friedman, KL, Cech, TR 1999, ‘Essential functions of amino-terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants’ Genes Dev. 13: 2863–2874. Kelleher, C, Teixeira, MT, Forstemann, K, Lingner, J 2002, ‘Telomerase: biochemical considerations for enzyme and substrate’ Trends Biochem. Sci. 27: 572–579.

Lai, CK, Miller, MC, Collins, K 2002, ‘Template boundary definition in Tetrahymena telomerase’ Genes Development, 16: 415–420. Lin, J, Ly, H, Hussain, A, Abraham, M, Pearl, S, Tzfati, Y, Parslow, TG, Blackburn, EH 2004, A universal telomerase RNA core structure includes structured motifs required for binding the telomerase reverse transcriptase protein’ Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 41, October, pp. 14713-14718 Livengood, AJ, Zaug, AJ, Cech, TR 2002, ‘Essential Regions of Saccharomyces cerevisiae Telomerase RNA: Separate Elements for Est1p and Est2p Interaction’ Mol.

Cell. Biol. 22: 2366–2374 Peterson, SE, Stellwagen, AE, Diede, SJ, Singer, MS, Haimberger, ZW, Johnson, CO, Tzoneva, M. Gottschling, DE 2001, ‘The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku’ Nat. Genet. 27: 64–67. Shay, J, Zou, Y, Hiyama, E, Woodring, EW 2001, ‘Telomerase and cancer’ Human Molecular Genetics, vol. 10, no. 7, pp. 677-685. Skloot, R 2001, ‘The Marvels of Telomerase’ Hopkins Medical News, winter 2001, viewed 10 September 2007, http://www. hopkinsmedicine. org/hmn/W01/top. html.

Tzfati, Y, Knight, Z, Roy, J, Blackburn, E H 2003, A novel pseudoknot element is essential for the action of a yeast telomerase, Genes Development 17: 1779–1788. Vermolen, BJ, Garini, Y, Mai, S, Mougey, V, Fest, T, Chuang, TCY, Chuang, AYC, Wark, L, Young, IT 2005, ‘Characterizing the Three-Dimensional Organization of Telomeres’ Cytometry, 67A: 144-150. Zapulla, DC, Cech, TR 2004, ‘Yeast telomerase RNA: A flexible scaffold for protein subunits’ Proceedings of the National Academy of Sciences of the United States of America, vol.

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