TEL0MERASE A TALE OF LIFE.
Dr. Dwijesh Kumar
Panda.
M.D, PhD (Med)
A Conceptual Diagram Showing DNA
Polymerase
Telomerase
is an enzyme that adds DNA sequence repeats to the end of DNA strands in the
telomere regions, which are found at the ends of eukaryotic chromosomes. This
region of repeated nucleotide called telomeres contain non-coding DNA material
and prevents constant loss of important DNA from chromosome end .As a result of
every time the chromosome is copied only 100-200 nucleotides are lost, which
causes no damage to the organism’s DNA. Telomerase is a reverse transcriptase
that carries its own RNA molecule, which is used as a template when it
elongates telomeres, which are shortened after each replication cycle.
The existence of a
compensatory shortening of telomere (telomerase) mechanism was first predicted
by Soviet biologist Alexey Olovnokoy in 1973, who also suggested the telomere
hypothesis of aging and the telomere’s connection to Cancer. Telomerase was
discovered by Carol W. Greinder and Elizabeth Blackburn in 1984. Greinder and
Blackburn were awarded the 2009 Nobel Prize in Physiology or Medicine for their
discovery.
FACTS ABOUT TELOMERES AND TELOMERASE:-
The human body is an
organism formed by adding many organ systems together. Each organ contains
tissues designed for specific functions. Tissues are made of cells joined
together to perform special functions. Each cell is made of smaller components
called organelles, one of which is called nucleus. The nucleus contains
structures called chromosomes that are usually “packages” of all the genetic
information that is passed from parents to children. The genetic information or
“genes”. Our bodies must duplicate their cells. This process is called
mitosis. Mitosis is a process that
allows one parent cell to divide into two new “daughter” cells. During mitosis,
the cells make copies of their genetic material. Half of the genetic material
goes to each new daughter cell. Each chromosome has a special protective cap
called a telomere located at the end of its “arms”. Telomeres are controlled by
the presence of the enzyme telomerase.
A telomere is a repeating
DNA sequence at the end of body’s chromosomes. Telomeres function by preventing
chromosomes from fusing to each other. They function by preventing chromosomes
from losing base pair sequences at their ends. However each time a cell
divides, some of the telomere is lost (usually 25-200 base pairs per division).
When the telomere becomes too short, the chromosome reaches a “critical length”
and can no longer replicate. This means that a cell becomes “old” and dies by a
process called apoptosis.
Telomerase,
also called telomere terminal transferase, is an enzyme made of protein and RNA
subunits that elongates chromosomes by adding TTAGGG sequences to the end of
existing chromosomes. Telomerase is found in foetal tissues, adult Germ cells
and also tumor cells. Telomerase activity is regulated during development and
has a very low, almost undetectable activity in somatic (body) cells. Because
these somatic cells do not regularly use telomerase, they age. The result of
aging cells is an aging body. If telomerase activated in a cell, the cell wall
continue to grow and divide. This “immortal cell” theory is important in two
areas of research aging and cancer.
Cellular aging, or senescence, is the
process by which a cell becomes old and dies. It is due to the shortening of
chromosomal telomeres to the point that the chromosome reaches a critical
length. Our cells are constantly
aging. Cancer cells are a type of
malignant cells. The malignant cells multiply until they form a tumor that
grows uncontrollably. Telomerase has been detected in human cancer cells and is
found to be 10-20 times more active than in normal body cells. This provides a
selective growth advantage to many types of tumors. If telomerase activity was
to be turned off, then telomeres in cancer cells would shorten, just like they do
in normal body cells. This would prevent the cancer cells from dividing
uncontrollably in their early stages of development. In essence, preventing
telomerase from performing its function would change cancer cells from
“immortal” to “mortal”. Scientists are on the verge of discovering many
of telomerase secrets. In the future, their
research in the area of telomerase could uncover valuable information to combat
aging, fight cancer and even improve the quality of medical treatment in other
areas such as skin grafts, for burn victims, bone marrow transplants, and heart
disease.
Clinical Implication:-
A variety of
premature aging syndromes are associated with short telomeres. These include
Werner syndrome, Ataxia telangiectasia, Bloom syndrome and Fanconi anemia.
Exposure of T-lymphocytes from HIV – infected human donors to a small molecule
telomerase activity retards telomere shortening, increase proliferative
potential, and .importantly, enhances cytokine/chemokine production and
antiviral activity. The cancer cell has an activated telomerase, eliminating
the process of death by chromosome instability or loss, absence of
apoptosis-induction pathways, and continued activation of mitosis.
ADDITIONAL ROLES IN CANCER, HEART DISEASE
AND QUALITY OF LIFE:-
Additional roles of
telomerase per work by Elizabeth Blackburn et al , include the upregulation of
70 genes known or suspected in cancer’s growth and spread through the body, and
the activation of glycolysis, which enables cancer cells to rapidly use sugar
to facilitate their programmed growth rate (roughly the growth rate of a
fetus).Blackburn et al has shown work that reveals that mothers caring for
their very sick children have shorter
telomeres when they report that their emotional stress is at the
greatest point. Cancer is a very difficult disease to fight, because the immune
system has trouble recognizing it. Because telomerase is necessary for the
immortality of so many cancer types, it is thought to be a potential drug
target. If a drug can be used to turn off telomerase in cancer cells, the above
process of telomere shortening will resume – telomere length will be lost as
the cells continue to divide, mutations will occur, and cell stability will
decrease. Some inherited diseases are now known to be caused by telomerase
defects such as congenital aplastic anemia, in which insufficient cell division
in the stem cells of the bone marrow lead to severe anemia.
Bad Genes and short telomeres
Bad Genes and Short Telomeres , Genetics influences Aging-
Controlling your genetics can help
you avoid the major age related diseases. The function of the genes can rebuild
the chromosomes. The chromosomes, the little rascals, have small substances at
the ends called telomeres. Every time a cell reproduces, that telomere gets a
little shorter. Once the protective covering on the tip is gone, the DNA begin
to fray. That is what causes cells to stop dividing and growing and
replenishing the body. The cell realizes that it is no longer helping the body
and commits suicide ( that is called apoptosis), which can contribute to age
related conditions. The body has a protein- called telomerase- that
automatically replenishes and rebuilds the ends of the chromosomes to keep
cells healthy. Telomerase is overactive in 85% of cancers. Cells to divide help
the cancer cells reproduce and spread. Researchers have found that chronic
stress can have a huge influence on how cells divide or fall to it. If stress
can be reduced one can increase the chance of rebuilding the telomeres and
decrease the odds of having the cells die and contribute to age related
problems. Because each of us has a unique genetic fingerprint, the detection,
prevention and treatment of diseases can be difficult. But as we start to
unlock the ways that we and the modern medicine can dramatically manipulate our
genes, we are going to start seeing how we can make our genes work for us, not
against us. Perhaps the best example of how genes affect us in our memory, which is goal one- in part so we can remember
the rest.
In conclusion, the
discoveries of Blackburn, Greider and Szostak have added a new dimension to our
understanding of the cell, shed light on disease mechanisms, and stimulated the
development of potential new therapies.
REFERENCES:-
1.
Cancer
1995-12-186 Am.J.Path.
2.
AJSP
2002-26-938
3.
Compositae
by ERNEST B.BABCOCK, University of California, USA.
4.
You
Staying Young- Michael F. Roizen, M.D.
Dr Dwijesh Kumar Panda
Filariologist & Pathologist
M5/12, Acharya Vihar
Bhubaneswar,751013
Cell:9438470777
Submitted to the Editor ,”Science Horizon” for favour of Publication
Dr. D K panda
Filariologist & Pathologist
M5/12, Acharya Vihar
Bhubaneswar,751013
Cell:9438470777
Submitted to the Editor ,”Science Horizon” for favour of Publication
Dr. D K panda