Telomere is the end part of the eukaryotic chromosomes and they need special way to replicate theirselves because of regular DNA replication can’t replicate the ends of eukaryotic chromosomes.
2. What are Telomeres
• Telomeres are the repetitive nucleotide
sequences that cap the ends of
chromosomes.
• Most of the chromosome, a portion of
telomere in maintained in a single stranded
form.
3. What are Telomeres Continued
• Most of telomeres are having single repeating sequence varies
from organism to organism.
4. Why Telomeres are important
• Telomeres are bound by number of proteins
• These proteins distinguish ends of chromosomes from sites of
chromosome breakage and other DNA brakes in the cell.
• These telomeres act as specialized origins of replication, that allow
the cell to replicate the end of chromosomes.
5. The DNA Replication
• DNA replication is a semi
conservative process
• It always happen from 5’ to 3’
end
• Because of this, there are two daughter strands are called leading
strand and lagging strand
6. The DNA Replication Continued
• For the replication starts need RNA
primers, leading strand need only one RNA
primer
• But lagging strand need multiple primers, In
this situation can’t replicate lagging strand
completely.
• But at the last Okazaki fragment can’t fill its
gap, at the end this creates incompletely
replicated DNA daughter strand
7. The end replication problem
• This problem called as end replication problem of DNA
• Because of incomplete replication of DNA cause to loss of some
genes from daughter cells
• When this happen several times complete loss of genes would
happen
8. How to solve this
“End Replication Problem”
• Organisms solve this end replication problem in variety of ways.
1. Use protein instead of RNA primer for last Okazaki fragment
2. Use of telomeres (most of eucaryotic chromosomes are use
this structure for replication of end of chromosomes)
9. Use of telomeres for
“end replication problem”
• Telomeres are the end parts of eukaryotic chromosomes.
• This part composed repeats of T&G rich DNA sequence and
each chromosome 3’ end extend beyond the 5’ end as single
stranded DNA.
10. Use of telomeres for
“end replication problem”
Continued…
• This unique extension structure act as origin of end replication.
• Also, this origin interact only with specialized DNA polymerase
called “Telomerase”
11. Telomerase Enzyme
• This enzyme includes multiple protein subunits and an RNA
component.
• Like all other DNA polymerase enzymes telomerase extend
DNA molecule from 5’ to 3’ end.
• But this enzyme does not need any parental DNA Template to
do so.
12. Telomeric replication process
• Telomerase enzyme has an RNA component that serve as the
template for adding the telomeric sequence to the 3’ end of the
chromosome.
• This is called as RNA
templated DNA
synthesis mechanism
occurs via Reverse
transcription
13. Telomeric replication process
NEW RNA
PRIMER
• Then using RNA primase enzyme and DNA polymerase bring
complementary RNA primer and replication done from 5’ to 3’
end
14. Telomeric replication process
• Because of the telomerase sequence replicate from the
telomeric RNA there is no information copied from parental
strand to daughter strand,
• But complete replication of linear DNA done by this process
15. Telomerase regulation
• The extension by telomerase enzyme could theoretically go on
unlimited length.
• This is regulated by proteins bounded to double stranded
regions of the telomeres
16. Telomerase regulation
• When few number of proteins are bounded to telomeres, 3’ end
of telomere can extend.
• As the telomere become longer more telomere binding proteins
are accumulating and more inhibition of 3’ extension. (Kind of
negative feedback)
17. Telomere Binding proteins protect
Chromosome ends
• Usual breakage ends of chromosomes act as recombination
sites and initiate natural recombination.
• Telomere binding proteins distinguish the end of chromosomes
from other DNA ends and protect from recombination
18. T-loop of telomeres
• Single stranded 3’ end of telomere invading the double stranded
region formed a loop like structure
• This masking the DNA end and
protecting from recombination
and, also relevant to telomere
length control
19. Aging, Cancer, and Telomere
Hypothesis
• The Telomere Hypothesis is a biological theory that suggests
that the shortening of telomeres
• In past studies found that cells are motile and even in isolation
studies cells can divide only a limited number of times
• At that time assume there was a countdown clock molecule in
cells and that limits the number of divisions the cell can done.
20. Aging, Cancer, and Telomere
Hypothesis
• After years of molecular studies scientists realize that unknown
countdown clock molecule could be telomeres.
• But this concept is still a hypothesis but there are many studies
that support this hypothesis
