**Author details**

problem of older donor tissue is its lower ability to endure stress and repair. Preexisting aging may reduce repair and survival capacity, and post-transplant stress such as rejection exhausts further this capacity, leading to graft failure [68]. Ischemia and reperfusion during transplan‐ tation lead to a temporary increase of reactive oxygen species in the organ, which are pre‐ dominant inducers of DNA breaks. Oxidative DNA damage advances telomere shortening [94]. Furthermore, sustained cellular turnover in chronic liver disease accelerates cellular senescence [2-4, 65-66]. The confluence of acute stress, oxidative stress, ageing, and senescence suggests possible mechanisms leading to graft failure. Avoidance of factors associated with oxidative stress and telomere dysfunction is recommended in association with current liver transplantation techniques. Telomeres in grafted livers may elongate somewhat longer if the grafts are immunologically well controlled [105]. Taken together, telomere length is one of the

available indicators for evaluation of liver allograft status (Fig.1).

8 Telomere - A Complex End of a Chromosome

**Figure 1.** Allograft failure and telomere dysfunction

Tatsuaki Tsuruyama\* and Wulamujiang Aini

\*Address all correspondence to: tsuruyam@kuhp.kyoto-u.ac.jp

Department of Pathology, Center for anatomical and Pathological Research, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto Prefecture, Japan

The authors have declared no conflicts of interest.

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**Chapter 2 Provisional chapter**

#### **Telomere and Telomerase in Cancer Telomere and Telomerase in Cancer**

Angayarkanni Jayaraman, Kalarikkal Gopikrishnan Kiran and Palaniswamy Muthusamy Angayarkanni Jayaraman, K.G. Kiran and Palaniswamy Muthusamy Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64721

#### **Abstract**

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16 Telomere - A Complex End of a Chromosome

55-59.

journal.pone.

The linear ends of chromosome are protected by specialized ribonucleoprotein (RNP) termed as telomere. These specialized terminal elements with tandem repeated sequence are the protective cap that alleviate end replication problem and cell senescence. The telomere length maintenance is essential to avoid cell death and apoptosis. Telomere shortening has been related to chronic stress due to several factors, which include not only psychological stress but also diseases such as cardiovascular diseases and cancer. Telomerase enzyme which maintains telomere length is the major factor responsible for evading cell death. Telomere length maintenance and telomerase expression put together are the prerequisite for immortality, an essential character for cancer cells. Understanding the mechanism of telomere and telomerase functions paves way for eradicating the diseases such as cancer.

**Keywords:** telomere length, telomerase, tumor progression, tumor immortality

#### **1. Introduction**

Telomeres are specialized DNA structures consisting of tandem arrays of hexa-nucleotide (TTAGGG) DNA sequences that cap the end of chromosomes. These structures residing near the ends of chromosomes play a very vital role in maintaining the integrity of the whole genome and prevent the loss of genetic material. As a consequence of cell division, short stretches of DNA will be lost from telomeric region and eventually lead to cellular senescence and death. There are a lot of evidences to suggest that telomere length is a better biomarker for overall health status, compared to the currently used biomarkers for the same. Few of the phenomena regarding the telomere length are unanswered till now. Till date it is unclear about the mechanistic

© 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. © 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.

regarding the telomere length are unanswered till now. Till date it is unclear about the mechanistic correlation between telomere size and life span of various species. To prevent senescence of cell, the preservation of telomere length is essential, which is maintained by telomerase enzyme. Telomerase is a reverse transcriptase enzyme which has recently emerged as an attractive target for cancer as it is a crucial factor required for the tumor immortalization of a subset of cells, including cancer stem cells. Studies have proved that 80–85% of the tumor cells express telomerase whereas somatic cells lack the expression of telomerase [1]. The important paradox is that telomerase-negative normal cells have lengthier telomeres than telomerase-positive cancer cells [2]. Thus difference in telomere length and cell kinetics between normal and cancerous cells shows that targeting telomerase is a more effective way to target cancer cells. Owing to the significant role of telomere and telomerase in tumor immortalization understanding their amassed influence on cancer is crucial for cancer therapy. In this context, this book chapter is focused on disseminating the integrated impact of telomere and telomerase on cancer progression.
