Telomerase 1

Telomerase
Jonathan Reyna
Cal State Fullerton University
Telomerase 2

Introduction

Telomerase is an enzyme that adds a repeating nucleotide sequence to the ends of DNA
to protect the ends of chromosomes. This protein appears at the end of DNA replication to add to
the end of the DNA, forming telomeres of DNA. Telomeres are the end of chromosomes that
contain a repeating nucleotide sequence. They protect the ends of DNA from erosion after
several rounds of replication. The telomeres act like staples for paper, holding the DNA together
in turn making sure the chromosome does not fall apart. Telomerase is a ribonucleic protein
containing components from RNA and protein. As a person ages their telomeres length
decreases, and it can leave the DNA susceptible to damage or mutations. Telomere length can
shorten a persons life by deteriorating faster. Plenty of research has been done to find
out how to slow down the regression of the telomeres length.

Discovery

In 1938 Hermann J. Muller, a geneticist, did not truly discover telomerase, but he noticed
a strange phenomenon within the fly species he was working with. In the Drosophila
melanogaster he found that the ends of the chromosomes were different from the rest of the
DNA. The ends could not be altered by way of deletions or insertions of nucleotides. The reason
he discovered was because of a protective cap at the end that he identified as the terminal gene,
or as it is now referred to as the telomere (Chuaire 2006). Then in 1975 two scientist Elizabeth
Blackburn and Joseph Gall studied eukaryotic organisms and found in the telomere region there
was a repeating sequence of six nucleotides. To further this research Blackburn and Jack
Szostak, a biologist, trying to create their own telomere implanted human genes into yeast
plasmids. They could recreate the sequence forcibly, so they concluded that there must be
an enzyme that functions to carry out the job (Chuaire 2006). Upon further testing, they
discovered the enzyme, telomerase, and how it functions. They also uncovered its relation with
Telomerase 3

the aging process and cancer, thus rewarding them with a Nobel Prize in 2009 for the importance
of their research (Corey 2009).

Structure

http://www.haematologica.org/content/92/8/1009
The telomerase is made of both RNA and protein components making this enzyme a
ribonucleoprotein. The protein part is called the telomerase reverse transcriptase (TERT), and the
RNA part is called the telomerase RNA (TERC). It is considered as a reverse transcriptase
because it can make a single DNA strand with the given RNA sequence in the enzyme
(Telomerase 2017). The TERT is made of four functional domains known as the N-terminal
domain (TEN), the TERT RNA binding domain (TRBD), the reverse transcriptase domain (RT),
and the C-terminal extension. However, it should be noted there are no known species with a
TERT containing all four domains (Zhang, Kim, Feigon 2011). These given parts allow the
protein to bind to the part of DNA that need to be capped off. They also give the telomerase the
function to add other proteins to the complex as well to perform its function. Telomerase is not
made by a single gene but by several and is constructed together in pieces. The TERT is made
from 1132 amino acids and then folded together. The TERT is then pieced together to the TERC
which is a non-coding RNA sequence that is 451 nucleotides long (Telomerase 2017).
Process
Telomerase 4

At the end of DNA replication the ends of the DNA strand is left exposed. The basic
function of telomerase is to protect these ends. Telomerase must add repeating sequences to act
as a cap for the DNA. In DNA replication a double strand of DNA will be made into two
daughter strands. The exposed ends are produced because after replication the 5end of the
DNA is not long enough to cover the 3 end. (B. 2016) The 3 end comes from the lagging strand

https://en.wikipedi
a.org/wiki/Telomerase
and the primer applying the nucleotides to the 5 end could not cover that region. This creates a
3 overhang on the DNA and if left the double strand would be at risk of coming apart. Or
another glaring issue is that the daughter strands of DNA would become smaller through each
replication and over time some genes could be eroded. The enzyme responsible for the
elongation process in replication, DNA polymerase, is not capable of adding any nucleotides to
cover the 3 overhang. To fix the problem telomerase will bind to the 3 overhang and proceed to
elongate it further with a repeating sequence (B. 2016). The sequence contains a random
sequence of 6 nucleotides that is non-coding so no proteins can be made from it (Telomerase
2017). The amount of times the sequence is repeated is different between each individual
Telomerase 5

extending from 100 to 1000 plus times. Once the telomerase has done its job in extending the 3
end DNA polymerase can finish replication. The enzyme will cover the 3 end with the
complementary nucleotides (B. 2016).

Mutations
 Telomerase is a necessary enzyme that protects our DNA, but as we age the protein does
slow down. The consequence is that our DNA will become shorter exposing the genes at these
sites to eroding. In a cell when the DNA reaches this point the cell will proceed to die off, but as
we get older this process is amplified because of decades of replication and shorter telomeres.
This can leave the DNA vulnerable to mutations in the DNA which in turn can cause cancer.
Mutations to telomerase has also been reported. Mutations to the genes that make
telomerase has caused three diseases within humans knowns as dyskeratosis congenita (DKC),
aplastic anemia (AA), and idiopathic pulmonary fibrosis (IPF) (Telomerase-Database 2013). In
DKC patients exhibit deletions or substitutions of nucleotides in the TERC gene and from this all
show short telomerase. Patients then experience shortened lifespans and die from bone marrow
failure. The short telomeres cause a high death cell count and lowers blood cells within the body.
The disease itself is rare and inherited (Garica, Wright, Shay 2017). Those suffering from AA
see mutations to both the TR and TERT genes. Patients also have a family history of blood
disease and ultimately die from bone marrow failure (Telomerase-Database 2013). Then in IPF
there have been mutations found on either the TERC or TERT genes. Individuals afflicted with
the disease has lung scarring or severe lung diseases.

Aging

Given telomerase relationship towards aging intensive research has been done to see if
any anti-aging application can be found from the protein. A study showed that mice with
increased activity of telomerase and adding to the length of telomeres also had increased risk of
cancer (Telomerase 2017). However, the exact opposite will have the same result. In the case
of using telomeres as an agent to increase our lifespan, there has not been any conclusive
research. The environment plays a factor in our telomere lengths. Increased stress on the body
causes increased DNA replication thus shorten the telomeres. Blackburn noted in her research
that these stresses include hormonal, oxidative, and inflammatory. These types of stresses will
accelerate the age of cells and increase cell death (Rehman 2014).

http://daunaru.com/moringa-is-the-key-to-anti-aging/

References
B. (2016, May 26). Telomere Replication - Boundless Open Textbook. Retrieved February 25,
2017, from https://www.boundless.com/biology/textbooks/boundless-biology-
textbook/dna-structure-and-function-14/dna-replication-101/telomere-replication-438-
11663/
Chuaire, L. (2006, September 8). Telomere and Telomerase: Brief review of a history initiated
by Hermann Mller and Barbara McClintock. Retrieved February 25, 2017, from
http://colombiamedica.univalle.edu.co/index.php/comedica/article/view/466/1053
Corey, D. R. (2009, December 24). Telomeres and Telomerase: From Discovery to Clinical
Trials. Retrieved February 25, 2017, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810624/
Garcia, C. K., Wright, W. E., & Shay, J. W. (2017). Human diseases of telomerase dysfunction:
insights into tissue aging. Nucleic Acid Research, 45(4). doi:10.1093/nar/gkm644
Rehman, J. (2014, July 5). Aging: Too Much Telomerase Can Be As Bad As Too Little.
Scientific Amercian. Retrieved February 25, 2017.
Telomerase. (2017, February 17). Retrieved February 25, 2017, from
https://en.wikipedia.org/wiki/Telomerase
Telomerase Database-Diseases. (2013, April 23). Retrieved February 25, 2017, from
http://telomerase.asu.edu/diseases.html
Zhang, Q., Kim, N., & Feigon, J. (2011, December 20). Architecture of human telomerase RNA.
PNAS, 108. doi:10.1073/pnas.1100279108

To start my definition, I wanted to partition the word into different sections so it would be much
easier to understand. I wanted to target an audience with a minor biological background so I
thought that defining the proteins structure and function were best to start with. Then I used
principle of operation by going through the proteins process within a cell. They would better
elaborate on the one sentence definition. After that I wanted to establish a relationship between
the protein and how it effects our everyday lives. I hoped that this would make a complex topic
interesting to readers. Then to finish the paper off I added graphics to help readers gain a better
understanding of how the protein works and what that process looks like.