In the intricate molecular world of life, a tightrope is constantly walked to maintain a delicate balance of physiological processes. As we delve into this captivating dance between life and death, we uncover the enzyme telomerase.

To understand the role of telomerase, we must first grasp the process of DNA replication. An enzyme called DNA polymerase III adds DNA nucleotides (the building blocks of genetic information) onto a short sequence of RNA nucleotides. DNA polymerase III can only add onto an existing RNA primer and can only add nucleotides in the 5’ carbon to 3’ carbon direction. Due to the antiparallel structure of DNA, the leading strand of DNA is replicated by following the “unzipping” of the DNA in the 5’ to 3’ direction while the lagging strand of DNA is replicated in the opposite 3’ to 5’ direction. The lagging strand is built with multiple RNA primers in a series of short segments called Okazaki fragments.

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Although it has not been experimentally demonstrated yet, scientists have reason to believe in the End Replication Problem Hypothesis: the lagging strand is not copied to the end of the DNA template given there is no known mechanism for the most distal RNA primer to be replaced by DNA. This leaves a sequence of DNA that has not been copied left out of the newly replicated strand. Therefore, every time DNA is replicated, the DNA sequence shortens slightly. Cells have managed around this fatal flaw with telomeres, which are structures of proteins and DNA found at the end of chromosomes. Telomeres have non-coding, repeating patterns of DNA that allow cells to divide 40-60 times before valuable genetic information itself begins to shorten. As the telomere becomes too short, it signals the DNA damage response which causes the cell to stop dividing or initiate apoptosis (programmed cell death). Scientists correlate the shortening of telomeres to age because the apoptosis of cells causes damage to tissues and organs.

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The role of telomerase is to slow the progression of the shortening of telomeres. Through reverse transcription, telomerase uses RNA to elongate DNA overhang to complete and extend DNA. Fatal conditions such as bone marrow failure, idiopathic pulmonary fibrosis, and dyskeratosis congenita occur when cells do not have enough telomerase. Additionally, studies have shown how lab mice become infertile and die early from symptoms of old age after generations without telomerase. This information begs the question: How come cells don’t produce more telomerase if it slows aging?

Telomerase is a double-edged sword. While low concentrations of telomerase are beneficial to prolonging the lifetime of cells, too much does more harm than good. Excessive concentrations of telomerase result in uncontrolled and unlimited cell proliferation. Unlimited cell proliferation may sound positive, but this phenomenon is known as cancer. Up to 80% of cancer cells have abnormally high levels of telomerase since it allows cells to bypass this limit, proliferating indefinitely without senescence or apoptosis. Cancer cells create tumors that metastasize, invading many parts of the body and hindering normal structure and function. Therefore, it is essential that cells maintain low levels of telomerase so as to suppress the development of cancer.

The dual nature of balancing between the promotion of cellular longevity and the potential for unchecked proliferation is an important one for the tiny but mighty enzyme telomerase.

Works Cited
Cong, Y.-S., et al. “Human Telomerase and Its Regulation.” Microbiology and Molecular Biology Reviews, vol. 66, no. 3, 1 Sept. 2002, pp. 407–425, https://doi.org/10.1128/mmbr.66.3.407-425.2002.
Ohki, R., et al. “In Vitro Reconstitution of the End Replication Problem.” Molecular and Cellular Biology, vol. 21, no. 17, 1 Sept. 2001, pp. 5753–5766, www.ncbi.nlm.nih.gov/pmc/articles/PMC87295/, https://doi.org/10.1128/mcb.21.17.5753-5766.2001.
RepeatDx. “How Telomere Shortening Affects Aging.” Www.youtube.com, 25 Nov. 2021, www.youtube.com/watch?v=pluI6SOd-_I. Accessed 17 Oct. 2022.
---. “The Links between Telomerase and Aging.” Www.youtube.com, 25 Nov. 2021, youtube.com/watch?v=7bbVDZ4DF78. Accessed 3 Mar. 2024.