**1. Introduction**

#### **1.1. Importance of telomeres**

Telomeres are specialized functional complexes that protect the ends of eukaryotic chromosomes. The telomeric DNA sequences are, in most species, tandem repeats of a short hexameric sequence unit [1]. Overall, telomere sizes range from about 15 to 20 kbp at birth to sometimes less than 5 kbp in chronic disease states. Telomeric repeats help maintain chromosomal integrity [2].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Evolutionary conservation of this repetitive DNA sequence family might indicate that sequence is essential to the cellular function [3]. Telomeric DNA sequences and structure are similar among otherwise widely divergent eukaryotes. The telomeric repeat unit is TTAGGG for humans as well as other vertebrates [4]. The ends of telomeres are protected and regulated by telomere binding proteins and form a t loop structure [2, 5]. Mainly, the inability of DNA polymerase to replicate the end of the chromosome during lagging strand synthesis results in the loss of telomeric repeats when cell divides. This phenomenon eventually results in a growth arrest and telomeres become critically shortened when multiple chromosome end fusions occur, resulting in a loss of cell viability [2]. Telomere shortening provides a barrier to cancer progression by preventing immortalization and the majority of the cancer cells depend on the activation of telomerase to gain proliferative immortality [2, 6]. But on the other hand, telomere shortening correlates with cellular aging. Stem and progenitor cells express low levels of telomerase [6].

#### **1.2. Telomerase structure and function**

Greider and Blackburn identified a specialized DNA polymerase in extracts from the *Tetrahymena* that extends the chromosome ends in eukaryotes [7]. Telomerase adds multiple copies of certain DNA unit to the terminal portion of one strand of the repeat tract [1, 4]. This process is required for genomic stability and cell viability. Telomerase is a specialized reverse transcriptase. Telomerase subunit TER identified in the late 1980s and catalytic subunit TERT in 1997. Subsequent studies showed that the TER and TERT together form a tight complex that is sufficient for telomeric DNA repeat synthesis *in vitro* [6]. TER contains RNA template for reverse transcription [8–10]. TERT contains discrete domains that carry out the mechanically complicated reaction of nucleic acid and nucleotide binding and selectivity in a coordinated manner during telomerase replication [8]. Despite only TERT and TER are required for telomerase catalytic activity *in vitro*, the physiologically functional holoenzyme is a multisubunit ribonucleoprotein (RNP). *Tetrahymena* telomerase holoenzyme contains eight subunits, each of which is essential for telomere length maintenance [10].

Telomerase is a very important enzyme for the aging process and carcinogenesis. Primary human cells exhibit limited replicative potential but the cancer cell lines are immortal with passage in culture [11]. In embryonic stem cells telomerase is activated and maintains telomere length but the level of telomerase activity is low or absent in the majority of the stem cells. Thus, even in stem cells, except embryonic stem cells and cancer stem cells, telomere shortening occurs, possibly at a slower rate than that in normal somatic cells [12].

To grow indefinitely, human cancer cells must compensate the progressive loss of telomeric DNA by cell division [13]. This immortality is mainly a result of telomerase activity. Telomerase is expressed in more than 85% of cancer cells [14–17], but in some cells, the telomere length could be maintained in the absence of telomerase. It has been deduced that one or more alternative telomerase-independent mechanisms exist in human cells [13].
