Transcript Telomeres and Telomerase in Cancer

Telomeres and
Telomerase in
Cancer
By Tara Lynn
What is a telomere?

A telomere is the end
structure of a
chromosome.

Telomeres are essential
regulators of both cell life
span and chromosomal
integrity.
[email protected], University of Texas, Southwestern Medical Center
Why do we need telomeres?
Telomerase Demo created by Dr. Donald F. Slish at SUNY, Plattsburgh
What is the structure of a
telomere?

All telomeres are composed of large
arrays of short guanine-rich sequences,
such as those found in mammalian cells,
5’-TTAGGGG-3’. (Hahn. Journal of Clinical
Oncology, vol21, no10, pp2034-2043)
Structure of Telomere
http://www.erin.utoronto.ca/~w3bio/JBC372/lecture06_2004/sld035.htm

Telomeres in embryonic cells, germ cells,
and cells that require extended
regenerations are long.

All other cells have short telomeres.

With each cell division telomeres become
shorter, until after dozens of divisions
telomeres get lost and the cell eventually
dies. (Bodnar et al. (1998) Science 279,
349-352).
What is Telomerase?

In the germ line and in
rapidly dividing somatic
cells, telomerase, a
reverse transcriptase that
contains an RNA
template, adds TTAGGG
repeats to chromosome
ends. Lodish et. al.

Telomerase is detectable
in the majority of cancer
cell lines and tumors.
[email protected], University of Texas, Southwestern Medical Center
Telomeres and Telomerase can
both suppress and cause cancer.
Tumor
Suppression
Tumor Promotion
Telomere Loss
Telomerase Activation
Limits cell
lifespan
(telomeres long)
Protects chromosome ends (?)
Induces genomic
instability
(telomeres short)
Promotes immortalization
What happens to an organism with
dysfunctional telomerase?

The results are mixed
Option 1: defects and aging
Progressive defects in cells with high
turnover (immune, hematopoietic, and
reproductive organs) in knock out mice.
Nature April 9, 1998
 Dyskeratosis congenita in humans:
premature organ failure, cancer
predisposition (Hahn 2003)

Option 2: Nothing happens for
several generations

After five or six generations, telomere loss
in mice leads to sterility. (Greider 1997)

mice that lack telomerase activity and
show short telomeres are tumor resistant,
except when the p53 tumor suppressor
protein is absent. (Blasco 2001)