Replication of the Ends of Eukaryotic Chromosome - Role of Telomerase

KASHMEERA.N.AKASHMEERA.N.A
III SEM MSc ZOOLOGYIII SEM MSc ZOOLOGY
ROLL NO : 37ROLL NO : 37
CHRIST COLLEGECHRIST COLLEGE
Replication of the Ends of Eukaryotic Chromosome - Role of Telomerase
WHAT ARE TELOMERES ?WHAT ARE TELOMERES ?
Telomeres are the ends of chromosomes
• Telomeres are repetitive nucleotide sequencesTelomeres are repetitive nucleotide sequences
located at the termini of linear chromosomeslocated at the termini of linear chromosomes
of most eukaryotic organisms.of most eukaryotic organisms.
• Its name is derived from the Greek nounsIts name is derived from the Greek nouns
telos ='end' and merοs = 'part’.telos ='end' and merοs = 'part’.
• Most prokaryotes do not have telomeres.Most prokaryotes 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 & TRF2Telomere specific proteins, eg. TRF1 & TRF2
bind to the repeat sequence and protect thebind to the repeat sequence and protect the
ends.ends.
• Without these proteins, telomeres are actedWithout these proteins, telomeres are acted
upon by DNA repair pathways leading toupon by DNA repair pathways leading to
chromosomal fusions.chromosomal fusions.
• While replicating DNA, the eukaryotic DNAWhile replicating DNA, the eukaryotic DNA
replication enzymes cannot replicate thereplication enzymes cannot replicate the
sequences present at the ends of thesequences present at the ends of the
chromosomes .chromosomes .
• Hence, these sequences and the informationHence, these sequences and the information
they carry may get lost.they carry may get lost.
• Telomeres "cap" the end-sequences andTelomeres "cap" the end-sequences and
themselves get lost in the process of DNAthemselves 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 nearRNA primer near
end of theend of the
chromosome onchromosome on
lagging strand can’tlagging strand can’t
be replaced withbe replaced with
DNA since DNADNA since DNA
polymerase mustpolymerase must
add to a primeradd to a primer
sequence.sequence.
Replication of the Ends of Eukaryotic Chromosome - Role of Telomerase
TELOMERASETELOMERASE
• Telomeric sequence is maintained by a specialTelomeric sequence is maintained by a special
enzyme called telomerase.enzyme called telomerase.
• SpecializedSpecialized reverse transcriptase.reverse transcriptase.
• Carries its own template RNA , which isCarries its own template RNA , which is
complementary to telomeric repeat sequences.complementary to telomeric repeat sequences.
Telomerase "replenishes" the telomere "cap" of the DNATelomerase "replenishes" the telomere "cap" of the DNA
• In most multicellular eukaryotic organisms,In most multicellular eukaryotic organisms,
telomerase is active only in germ cells, stemtelomerase is active only in germ cells, stem
cells, and certain white blood cells.cells, and certain white 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 RNARemoval of the RNA
primer leaves an overhanging 3' end ofprimer leaves an overhanging 3' end of
chromosomal DNA, which canchromosomal DNA, which can
form loops at the ends of eukaryoticform loops at the ends of eukaryotic
chromosomeschromosomes
CLINICAL ASPECTSCLINICAL ASPECTS
•Many experiments haveMany experiments have
shown that there is a directshown that there is a direct
relationship betweenrelationship between
telomeres and aging, and thattelomeres and aging, and that
telomerase has the ability totelomerase has the ability to
prolong life and cell division.prolong life and cell division.
• Most somatic cells do not have sufficientlyMost somatic cells do not have sufficiently
high levels of telomerase to maintain thehigh levels of telomerase to maintain the
length of their telomeres for an indefinitelength of their telomeres for an indefinite
number of cell divisions.number of cell divisions.
• Consequently, telomeres gradually shorten asConsequently, telomeres gradually shorten as
cells age.cells age.
• This shortening eventually leads to cell deathThis shortening eventually leads to cell death
or senescence.or senescence.
• Cancer cells express abnormally high levels ofCancer cells express abnormally high levels of
telomerase, allowing them to continue dividingtelomerase, allowing them to continue dividing
indefinitely.indefinitely.
Replication of the Ends of Eukaryotic Chromosome - Role of Telomerase
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Replication of the Ends of Eukaryotic Chromosome - Role of Telomerase

  • 1. KASHMEERA.N.AKASHMEERA.N.A III SEM MSc ZOOLOGYIII SEM MSc ZOOLOGY ROLL NO : 37ROLL NO : 37 CHRIST COLLEGECHRIST COLLEGE
  • 3. WHAT ARE TELOMERES ?WHAT ARE TELOMERES ?
  • 4. Telomeres are the ends of chromosomes
  • 5. • Telomeres are repetitive nucleotide sequencesTelomeres are repetitive nucleotide sequences located at the termini of linear chromosomeslocated at the termini of linear chromosomes of most eukaryotic organisms.of most eukaryotic organisms. • Its name is derived from the Greek nounsIts name is derived from the Greek nouns telos ='end' and merοs = 'part’.telos ='end' and merοs = 'part’. • Most prokaryotes do not have telomeres.Most prokaryotes do not have telomeres.
  • 6. Repetitive DNA sequenceRepetitive DNA sequence (TTAGGG in vertebrates)(TTAGGG in vertebrates) Specialized proteinsSpecialized proteins Form a 'capped' end structureForm a 'capped' end structure TELOMERESTELOMERES
  • 7. • Telomere specific proteins, eg. TRF1 & TRF2Telomere specific proteins, eg. TRF1 & TRF2 bind to the repeat sequence and protect thebind to the repeat sequence and protect the ends.ends. • Without these proteins, telomeres are actedWithout these proteins, telomeres are acted upon by DNA repair pathways leading toupon by DNA repair pathways leading to chromosomal fusions.chromosomal fusions.
  • 8. • While replicating DNA, the eukaryotic DNAWhile replicating DNA, the eukaryotic DNA replication enzymes cannot replicate thereplication enzymes cannot replicate the sequences present at the ends of thesequences present at the ends of the chromosomes .chromosomes . • Hence, these sequences and the informationHence, these sequences and the information they carry may get lost.they carry may get lost. • Telomeres "cap" the end-sequences andTelomeres "cap" the end-sequences and themselves get lost in the process of DNAthemselves get lost in the process of DNA replication.replication.
  • 9. Telomeres are the ends of chromosomes  Protect ends  Maintain length
  • 10. THE END REPLICATION PROBLEMTHE END REPLICATION PROBLEM RNA primer nearRNA primer near end of theend of the chromosome onchromosome on lagging strand can’tlagging strand can’t be replaced withbe replaced with DNA since DNADNA since DNA polymerase mustpolymerase must add to a primeradd to a primer sequence.sequence.
  • 12. TELOMERASETELOMERASE • Telomeric sequence is maintained by a specialTelomeric sequence is maintained by a special enzyme called telomerase.enzyme called telomerase. • SpecializedSpecialized reverse transcriptase.reverse transcriptase. • Carries its own template RNA , which isCarries its own template RNA , which is complementary to telomeric repeat sequences.complementary to telomeric repeat sequences.
  • 13. Telomerase "replenishes" the telomere "cap" of the DNATelomerase "replenishes" the telomere "cap" of the DNA
  • 14. • In most multicellular eukaryotic organisms,In most multicellular eukaryotic organisms, telomerase is active only in germ cells, stemtelomerase is active only in germ cells, stem cells, and certain white blood cells.cells, and certain white blood cells.
  • 15. HOW TELOMERASE WORK ?HOW TELOMERASE WORK ?
  • 16. MECHANISM OF TELOMERASE ACTIONMECHANISM OF TELOMERASE ACTION TetrahymenaTetrahymena Model organism used in telomere & telomerase research.Model organism used in telomere & telomerase research.
  • 17. MECHANISM OF TELOMERASE ACTIONMECHANISM OF TELOMERASE ACTION
  • 18. Removal of the RNARemoval of the RNA primer leaves an overhanging 3' end ofprimer leaves an overhanging 3' end of chromosomal DNA, which canchromosomal DNA, which can form loops at the ends of eukaryoticform loops at the ends of eukaryotic chromosomeschromosomes
  • 20. •Many experiments haveMany experiments have shown that there is a directshown that there is a direct relationship betweenrelationship between telomeres and aging, and thattelomeres and aging, and that telomerase has the ability totelomerase has the ability to prolong life and cell division.prolong life and cell division.
  • 21. • Most somatic cells do not have sufficientlyMost somatic cells do not have sufficiently high levels of telomerase to maintain thehigh levels of telomerase to maintain the length of their telomeres for an indefinitelength of their telomeres for an indefinite number of cell divisions.number of cell divisions. • Consequently, telomeres gradually shorten asConsequently, telomeres gradually shorten as cells age.cells age. • This shortening eventually leads to cell deathThis shortening eventually leads to cell death or senescence.or senescence.
  • 22. • Cancer cells express abnormally high levels ofCancer cells express abnormally high levels of telomerase, allowing them to continue dividingtelomerase, allowing them to continue dividing indefinitely.indefinitely.