Telomeres are the protective caps on chromosome ends found
in eukaryotic cells. They consist of DNA and associated proteins
that are essential for chromosome integrity and stability.
In human chromosomes, but also in other species, the telomeres
consist of thousands of copies of 6 base repeats
(TTAGGG) or very closely related repeats. Broken chromosomes
lacking telomeres undergo fusion, rearrangement and
translocation. In somatic cells, telomere length is progressively
shortened with each cell division, both in vivo and in vitro due
to the inability of the DNA polymerase complex to replicate
the very 5` end of the lagging strand of DNA.
In humans, Telomerase, the enzyme that maintains the ends
of chromosomes, is absent from the majority of somatic cells
but is present and active in most tumors. Telomerase is a
ribonucleoprotein that synthesises and directs the telomeric
repeats onto the 3` end of existing telomeres using its RNA
component as a template. Telomerase activity has been shown
to be specifically expressed in immortal cells, cancer cells, and
germ cells, where it compensates for telomere shortening during
DNA replication and thus stabilises telomere length.
These observations have led to a hypothesis that telomere
length may function as a mitotic clock to sense cell aging and
eventually signal replicative senescence or programmed cell
death. Therefore, expression of telomerase activity in cancer
cells is seen as a necessary and essential step for tumor development
Introduction of the telomerase catalytic protein component
into normal telomerase-negative human cells may result in
restoration of telomerase activity and extension of cellular life
span. Human cells with introduced telomerase maintain a normal
chromosome complement and continue to grow in a normal
manner. Therefore induction of Telomerase activity is
nowadays used to immortalize cell lines. Telomerase-induced
manipulations of telomere length may thus be important not
only for cell and tissue engineering but also for dissecting the
molecular mechanisms underlying inherited genetic diseases,
as well as defining the genetic pathways leading to cancer.
Because almost all human tumors express telomerase activity,
inhibition of telomerase may result in gradual erosion of
telomeres and eventual cessation of cell proliferation or induction
of apoptosis. Thus telomerase may also be a promising target
for cancer therapy.
TRAP assay – The development of a sensitive and efficient
PCR-based telomerase activity detection method, TRAP
(Telomeric Repeat Amplification Protocol), has made possible
large scale analysis of telomerase activity in human cells and
tissues. To date, telomerase activity has been detected in
almost all tumors.