It describes about Structure and function of telomere, Telomerase enzyme, How does telomerase works?, Telomere replication, What happens to telomeres as we age?, Factors contribute to telomere shortening

1. A SEMINAR PRESENTATION FOR PARTIAL FULFILLMENT
OF MASTER’S DEGREE IN BIOTECHNOLOGY
PRESENTED BY – ANKITAAGRAWAL
DEPARTMENT OF BT & BI,SU
MSC 4th SEM.
ROLL NO – 18 BT 01
REG. NO -38226/15
.

2. CONTENTS
• Introduction
• Structure of telomere
• Function of telomere
• Telomerase
• How does telomerase works?
• Telomere replication
• Whathappenstotelomeresasweage?
• Factors contribute to telomere shortening
• Why do telomeres get shorter each time a cell
divides?
• Conclusion

3. INTRODUCTION
• Telomeres (telos = end, meros = part)
• Repetitive nucleotide sequence (in human TTAGGG, 2500
timesrepeat).
• Present (EK) at the end of chromosome.
• Telomere loss is a major cause of cellular aging.
DISCOVERY
• Blackburn, Carol Greider and Jack Szostak were
awarded the 2009 Nobel prize in physiology and
medicine for the discovery of telomerase enzyme.

4. ** Act as cellular
aging clock

5. STRUCTURE OF HUMAN TELOMERE
• Conserved sequence.
• Length varies from 2 to 20 kb pairs (depending on
tissue type and human age).
• Consists of double stranded short tandem repeats
(TTAGGG), followed by terminal 3’-G rich single
stranded overhangs.
Fig.1 Telomeric DNA
single strand region
150-300 bases
Double strand region
5000-20000 bases

6. Conti….
• The telomere DNA is thought to adopt the T-loop
structure, where the telomere ends fold back on itself
and the 3’-G strand overhangs invades into the double
stranded DNA (the so called D-loop).
FIG.2.T-loop formation

7. Conti….
• Telomere can also fold into G-quadruplex (higher-order
DNA conformation, guanine rich).
• G-quadruplex is maintained by a set of telomeric protein
complex (SHELTERIN).
• Shelterin (telosome) consists of six individual proteins,
1) TRF1 ( Telomeric Repeat binding Factor 1)
2) TRF2 (Telomeric Repeat binding Factor 2)
3) TIN2 (TRF1 Interacting Protein 2)
4) TPP1 (Tripeptidyl-peptidase 1)
5) RAP-1 (Repressor-Activatior Protein 1)
6) POT1 ( Protection Of Telomere 1)
attach to double-
stranded
telomeric repeats
binds to the single-
stranded overhang.
act as bridging
proteins
inhibits DNA repair

8. Structure of human telomere

9. Telomere
function
Cellular
replication
Prevent
genomic
instability
Prevent
fusion
Protect from
cellular
senescence
Protect
genomic
integrity
Protect
from DNA
mutation
Mitochondrial
degradation

10. TELOMERASE
Reverse transcriptase(RT) in nature.
 Ribonucleoprotein (RNA +RNA
binding protein) that adds a species
dependent telomere repeat sequence to
3’ end of chromosome.
 Known as cellular immortalizing
enzyme.
 High telomerase activity exists in
germ cells, stem cells, epidermal skin
cells, follicular hair cells, and cancer
cells.

11. Telomerase structure
• The core enzyme consists of
a) TERT – telomerase reverse transcriptase
catalytic subunit
b) TERC/TR - telomerase RNA (recognizes -OH
group at 3’ end of G-strand overhang & elongates
the telomere)

12. Whathappenstotelomeresasweage?
• Chromosomes are shortened by about 20-200
bases per replication (i.e. telomere seq lost).
• Without telomeres, important DNA would be lost
every time a cell divides.
• This would eventually lead to the loss of
entire gene.
• Example,
human blood cells length of telomere,
At birth – 8000 bp
Adult – 3000 bp
old age – 1500 bp

14. Factors contribute to
telomere shortening
End replication
problem
Oxidative stress
**When the telomere becomes too short, the chromosome reaches a Critical
lengthandcannolongerbereplicated.
• This ‘critical length’ triggers the cell to die by a process called apoptosis, also
knownasprogrammedcelldeath.

15. • With each cell division, telomere length is
reduced by ~20 to 200 kb primarily because the
lagging strand of DNA synthesis is unable to
replicate the extreme 3’ end of the chromosome
which is denoted as End Replication Problem.
• Occurs during the DNA replication in Eukaryotes
only.
END REPLICATION PROBLEM

16.  Occurs during
the DNA
replication in
Eukaryotes only.

18. • If cells divide without telomeres, they would lose their ends of
chromosomes i.e. genetic information.
• Cells normally can divide only about 50-70 times; with
telomers getting progressively shorter until the cells become
senescent & die.
• Hence it has been proposed that telomere shortening function
as MOLECULAR CLOCK that COUNTS DOWN to the end of
cell division.
• This diminished ability of the cells to grow is strongly
associate with the aging process with the reduced cell
population directly contributing to weakness, illness and
organ failure.
CONCLUSION

19. FUTURE SCOPE
• Measuring telomerase may be a new way to detect
cancer (If scientists can learn how to stop
telomerase, they might be able to fight with cancer by
making cancer cells age and die).
• Some of the drugs are showed positive results by
inhibiting telomerase and associated proteins and
finding the way to shortening of telomere which
results in cell death/apoptosis.
• Most of anti-telomerase drugs are still in Clinical
phases I and II.

20. Reference
• https://www.intechopen.com/books/telomere-a-complex-end-
of-a-chromosome/telomere-and-telomerase-in-cancer
• Pathfinder (part-1)
• https://www.slideshare.net/fuad76/telomere-and-telomerase
• https://www.slideshare.net/sparkle23/telomere-69010963
• https://en.wikipedia.org/wiki/Telomerase
• https://en.wikipedia.org/wiki/Telomere
• Anna Rev. Biochent. 19%. 6S:337-65 by Carol W. Greider