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Telomeres

What are telomeres?


 Telomeres are…
• Repetitive DNA sequences at the ends of all
human chromosomes
• They contain thousands of repeats of the six-
nucleotide sequence, TTAGGG
• In humans there are 46 chromosomes and thus
92 telomeres (one at each end)
What do telomeres do?
 They protect the chromosomes.
 They separate one chromosome from
another in the DNA sequence
 Without telomeres, the ends of the
chromosomes would be "repaired", leading
to chromosome fusion and massive genomic
instability.
Telomere function, cont’.
 Telomeres are also thought to be the "clock"
that regulates how many times an individual
cell can divide. Telomeric sequences
shorten each time the DNA replicates.
Think of it like this….
 Telomeres effectively "cap" the end of a
chromosome in a manner similar to the way
the plastic on the ends of our shoelaces
"caps" and protects the shoelaces from
unraveling.
How are telomeres linked to
aging?
 Once the telomere shrinks to a certain level,
the cell can no longer divide. Its metabolism
slows down, it ages, and dies.
Telomeres & Aging
 Healthy human cells are mortal because
they can divide only a finite number of
times, growing older each time they divide.
Thus cells in an elderly person are much
older than cells in an infant.
Telomeres & Aging
 It has been proposed that telomere
shortening may be a molecular clock
mechanism that counts the number of times
a cell has divided and when telomeres are
short, cellular senescence (growth arrest)
occurs.
Telomeres & Aging
 It is believed that shortened telomeres in
mitotic (dividing) cells may be responsible
for some of the changes we associate with
normal aging.
What is telomerase
 Telomerase (TEE-LÓM-ER-ACE) is a
ribonucleoprotein enzyme complex that has been
referred to as a cellular immortalizing enzyme.
 It stabilizes telomere length by adding hexameric
(TTAGGG) repeats onto the telomeric ends of the
chromosomes, thus compensating for the erosion
of telomeres that occurs in its absence.
How Does Telomerase Work?
 Telomerase works by adding back
telomeric DNA to the ends of
chromosomes, thus compensating for the
loss of telomeres that normally occurs as
cells divide.
 Most normal cells do not have this enzyme
and thus they lose telomeres with each
division.
How Does Telomerase Work?
 In humans, telomerase is active in germ
cells, in vitro immortalized cells, the vast
majority of cancer cells and, possibly, in
some stem cells.
 High telomerase activity exists in germ
cells, stem cells, epidermal skin cells,
follicular hair cells, and cancer cells.
How Does Telomerase Work?
 Some cells are immortal because their
telomerase is switched on
 Cancer cells do not age because they
produce telomerase, which keeps the
telomere intact.

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