Telomerase

KASHMEERA-N-A 28,307 views 23 slides Jan 11, 2013
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KASHMEERA.N.AKASHMEERA.N.A
III SEM MSc ZOOLOGYIII SEM MSc ZOOLOGY
ROLL NO : 37ROLL NO : 37
CHRIST COLLEGECHRIST COLLEGE

WHAT ARE TELOMERES ?WHAT ARE TELOMERES ?

Telomeres are the ends of chromosomes

•Telomeres are repetitive nucleotide sequences Telomeres are repetitive nucleotide sequences
located at the termini of linear chromosomes located at the termini of linear chromosomes
of most of most eukaryoticeukaryotic organisms. organisms.
• Its name is derived from the Greek nouns Its name is derived from the Greek nouns
telos ='end' and merοs = 'part’. telos ='end' and merοs = 'part’.
•Most Most prokaryotesprokaryotes do not have telomeres. do not have telomeres.

Repetitive DNA sequenceRepetitive DNA sequence
(TTAGGG in vertebrates)(TTAGGG in vertebrates)
Specialized proteinsSpecialized proteins
Form a 'capped' end structureForm a 'capped' end structure
TELOMERESTELOMERES

•Telomere specific proteins, eg. TRF1 & TRF2 Telomere specific proteins, eg. TRF1 & TRF2
bind to the repeat sequence and protect the bind to the repeat sequence and protect the
ends.ends.
•Without these proteins, telomeres are acted Without these proteins, telomeres are acted
upon by DNA repair pathways leading to upon by DNA repair pathways leading to
chromosomal fusions.chromosomal fusions.

•While replicating DNA, the eukaryotic DNA While replicating DNA, the eukaryotic DNA
replication enzymes cannot replicate the replication enzymes cannot replicate the
sequences present at the ends of the sequences present at the ends of the
chromosomes .chromosomes .
•Hence, these sequences and the information Hence, these sequences and the information
they carry may get lost.they carry may get lost.
• Telomeres "cap" the end-sequences and Telomeres "cap" the end-sequences and
themselves get lost in the process of DNA themselves get lost in the process of DNA
replication.replication.

Telomeres are the ends of
chromosomes
Protect ends
Maintain length

THE END REPLICATION PROBLEMTHE END REPLICATION PROBLEM
RNA primer near RNA primer near
end of the end of the
chromosome on chromosome on
lagging strand can’t lagging strand can’t
be replaced with be replaced with
DNA since DNA DNA since DNA
polymerase must polymerase must
add to a primer add to a primer
sequence.sequence.

TELOMERASETELOMERASE
•Telomeric sequence is maintained by a special Telomeric sequence is maintained by a special
enzyme called telomerase.enzyme called telomerase.
•Specialized Specialized reverse transcriptase.reverse transcriptase.
•Carries its own template RNA , which is Carries its own template RNA , which is
complementary to telomeric repeat sequences.complementary to telomeric repeat sequences.

Telomerase "replenishes" the telomere "cap" of the DNA Telomerase "replenishes" the telomere "cap" of the DNA

•In most multicellular eukaryotic organisms, In most multicellular eukaryotic organisms,
telomerase is active only in telomerase is active only in germ cellsgerm cells, ,
stem cellsstem cells, and certain , and certain white blood cellswhite blood cells. .

HOW TELOMERASE WORK ?HOW TELOMERASE WORK ?

MECHANISM OF TELOMERASE ACTIONMECHANISM OF TELOMERASE ACTION
TetrahymenaTetrahymena
Model organism used in telomere & telomerase research.Model organism used in telomere & telomerase research.

MECHANISM OF TELOMERASE ACTIONMECHANISM OF TELOMERASE ACTION

Removal of the RNA Removal of the RNA
primer leaves an overhanging 3' end of primer leaves an overhanging 3' end of
chromosomal DNA, which can chromosomal DNA, which can
form loops at the ends of eukaryotic form loops at the ends of eukaryotic
chromosomes chromosomes

CLINICAL ASPECTSCLINICAL ASPECTS

•Many experiments have Many experiments have
shown that there is a direct shown that there is a direct
relationship between relationship between
telomeres and aging, and that telomeres and aging, and that
telomerase has the ability to telomerase has the ability to
prolong life and cell division.prolong life and cell division.

•Most somatic cells do not have sufficiently Most somatic cells do not have sufficiently
high levels of telomerase to maintain the high levels of telomerase to maintain the
length of their telomeres for an indefinite length of their telomeres for an indefinite
number of cell divisions. number of cell divisions.
•Consequently, telomeres gradually shorten as Consequently, telomeres gradually shorten as
cells age.cells age.
•This shortening eventually leads to cell death This shortening eventually leads to cell death
or senescence. or senescence.

•Cancer cells express abnormally high levels of Cancer cells express abnormally high levels of
telomerase, allowing them to continue dividing telomerase, allowing them to continue dividing
indefinitely. indefinitely.