I. Function and Purpose of Telomerase:

All organisms must undergo DNA replication in order to duplicate their DNA. This occurs by pairing complementary bases. During DNA replication, the two old DNA strands serve as templates for the formation of a new strand. For a more detailed overview, see this video.

During DNA replication, the ends of chromosomes are shortened because of the end-replication problem (Podlevsky et al 2008). This occurs because polymerase cannot transcribe the last primer of the lagging strand so the DNA at that spot is lost. To prevent this from happening, telomeres are added to the ends of DNA by telomerase. Telomeres are usually simple tandem repeats that contain no genetic information (Podlevsky et al 2008). Telomeres exist to maintain the integrity of the chromosome and to prevent unnecessary recombination and end to end joining (Tomlinson et al 2006).

 Telomere picture

Telomerase is made up of two different structures: a protein called TERT (telomerase reverse transcriptase) and a RNA template (Podlevsky et al 2008). The TERT protein synthesizes telomeric DNA repeats using a short sequence in the RNA template (Podlevsky et al 2008).

 Telomerase picture

For a summary of telomerase and telomeres, see this video: 

II. Structures

Secondary and Tertiary structures of the RNA component of telomerase have been found for many species including humans. Here is a comprehensive list (http://telomerase.asu.edu/structures.html).

III. Diseases related to Telomerase and why they occur

Most human somatic cells do not contain a high amount of telomerase or its activity is inhibited (Collins, K 2009). However, the majority of human cancer cells have been found to have active telomerase (Collins, K 2009).

     a. Dyskeratosis Congenita (DKC) is an inherited disease whose symptoms include hyperpigmentation (dark patches of skin), oral leukoplakia (white spots      inside the mouth), and lack of nails (http://telomerase.asu.edu/diseases.html). Individuals with this disease usually die from bone marrow failure,      immunodeficiency, pulmonary complications, or malignancies (http://telomerase.asu.edu/diseases.html). Cells of patients with the autosomal dominant or      X-linked form of this disease have a mutation that lowers the function of telomerase by 50% (Errington et al 2008). This lowering results in severe diseases      and early death (Errington et al 2008).

      Symptoms of dyskeratosis congenita

      Chart of dyskeratosis congenita

     b. Aplastic Anemia (AA) is more of an acquired disease than it is hereditary, although sometimes family history plays a part      (http://telomerase.asu.edu/diseases.html). This disease has connections with mutations in both the TERT protein and the RNA template of telomerase      (http://telomerase.asu.edu/diseases.html). Individuals with this disease usually die of bone marrow failure (http://telomerase.asu.edu/diseases.html).

      This is the bone marrow of a patient with Aplastic Anemia

     c. Idiopathic Pulmonary Fibrosis (IPF) is also caused by mutations to TERT and the RNA template of telomerase      (http://telomerase.asu.edu/diseases.html). This disease causes fibrotic lesion and scarring of the lung (http://telomerase.asu.edu/diseases.html). The      excess scar tissue results in decreased lung volume (http://telomerase.asu.edu/diseases.html).

      Scarring of the lung tissue (IPF)

     Pulmonary hypertension in a patient with IPF (Medical Journal)

IV. Therapeutic uses of telomerase

     a. It was found that short telomeres impair the function of epidermal stem cells, which causes impaired skin and hair growth (Siegl-Cachedenier et al 2007). To remedy this, a study has been conducted in which telomerase is reintroduced in mice with short telomeres to correct epidermal stem cell defects (Siegl-Cachedenier et al 2007).  This reintroduction of telomerase also results in a normal lifespan by preventing degenerative pathologies (Siegl-Cachedenier et al 2007).

     b. It has been found that transduction of the TERT protein can provide the autosomal dominant form of Dyskeratosis congenita with enough telomerase activity to extend the average length of telomeres (Westin et al 2008). It was also found that the expression of TERT and the RNA component together results in even more telomerase activity (Westin et al 2008). This is evidence that autosomal dominant DC cells can be saved from defects in telomere maintenance (Westin et al 2008). This method may be used for preventing the effects of telomere shortening in other diseases as well (Westin et al 2008).