2. CONTENT..
o Introduction
o History
o Structure of Telomeres
o Telomeric DNA sequence
o Structural proteins
o Function of Telomeres
o Telomere and aging
o Telomerase
o Reference
3. INTRODUCTION
Telomeres constitute the end of
chromosome. They are characterised by a
long series of short, tandemly repeated
sequences.
The type of sequence remains the same for
all eukaryotites. Thus, telomeres are
highly conserved region.
5. STRUCTURE OF TELOMERE
o The telomere has two types of known core
components:-
1. The telomeric DNA
2. Proteins
o Telomeric DNA binding proteins binds to
telomeric DNA through recognition of it’s
nucleotide sequences, and in turn bind other
protein complex.
6. TELOMERIC DNA SEQUENCE
At the telomeres the 3’ ends are little bit more elongated
than 5’ end about 14-16 nucleotide.
3’parental DNA strand
5’Lagging DNA strand
5’
3’
Primer removed
5’
3’
3’
5’
telomere
RNA primer
Okazaki fragment
7. It has a repeating unit TTAGGG and
that’s why the telomere towards the
3’end appears like a single stranded
structure.
As this sequence is rich in Guanine it
forms specific structures called ‘G-
quartets’.
8. STRUCTURAL PROTEINS
Some proteins bind to the double stranded region of
telomeres which are responsible for the stability of
chromosomes.
That proteins are:
1. TRF-1
2. TRF-2
o (TTAGGG Repeat Binding Factors 1 and 2) structurally
these two protein are related and posses similar domain
organisation.
9. Both the proteins associate with telomeres
thoughout the cell cycle and bind to telomeres as
homodimers.
The resulting nucleoprotein complex stabilizes
the end of DNA molecule and prevent it from
DNA damage.
Thus, TRF-1 and 2 provides stability to the
telomeres and thus the complete DNA.
TRF-2 is considered to be more effective than
TRF-1. Electron microscopy revealed that TRF-
2 proteins gives lariat like structure to the
telomere.
10. TELOSOME OR SHELTERIN
POT 1 (protection of telomeres 1)binds to the
sequence in single stranded form.
TIN1(TRF1- interacting protein) and TPP1
protein keep TRF1,TRF2 and POT1 together.
This 6 proteins complex, SHELTERIN prevents
the activation of the DNA damage response.
SHELTERIN is required for the recruitment of
telomerase.
11. FUNCTION OF TELOMERE
PROTECTION FROM DNA DAMAGE:
Telomeres prevents chromosome ends from being
mistaken for damage or broken DNA.
12. PROTECTION FROM RECOMBINATION
Ends of linear eukaryotic chromosomal DNA
that are broken or have incomplete telomeric
structures are subjected to fusion, by
nonhomologous recombination, to other broken
DNA ends (but not to functional telomeric
termine).The resulting dicentric and other
aberrent chromosome are deleterious because
they cannot segregate properly.
13. ROLES OF TELOMERES IN MEIOSIS
Early in meiotic prophase, telomere play the
distinctive function of anchoring chromosomes
to inner nuclear membrane. Subsequently, as a
consequence of the nuclear membrane
polirization,telomeres cluster together into
bouquet configuration, which facilitates pairing
and recombination of the homologous
chromosome.
14. TELOMERE AND AGING
After a certain number of cell
division, the telomere would be so
short a to somehow prevents the cell
from further proliferation- putting in a
state called senescense.
16. WHAT IS TELOMERASE?
Telomerase is the enzyme which maintains the
telomeres, also called as terminal transferase.
Telomerae is an unusual enzyme composed of
protein and RNA.
In case of humans, the RNA component is 450
nucleotide in length, and its 5’ terminal it
contains the sequence 5’-CUAACCCUAAC-3’.
The telomerase RNA sequence can be used as a
template for extension of telomere.
18. REFERENSES :-
James D watson: Molecular Biology of the Gene
Mapping and clonning of a human telomerase repressor
gene on chromosome 3’ Cooper
www.els.net encyclopedia of life science
yourgenome.org
Tascience.com
Spectracell.com