TELOMERES & THEIR APPLICATIONS

DNA AND TELOMERES

TECHNICALLY SPEAKING

• A telomere is a region of repetitive nucleotide

 sequences at each end of a chromatid, which

protects the end of the chromosome from

deterioration or from fusion with neighboring

chromosomes. Its name is derived from the Greek

nouns ‘telos’ meaning 'end' and ‘merοs’ meaning

'part.‘

IN PLAIN WORDS

• Telomeres have been compared with the

plastic tips on shoelaces, because

they keep chromosome ends from fraying and

sticking to each other, which would destroy or

scramble an organism's genetic information.

telomere

STRUCTURE, FUNCTION AND EVOLUTIONARY BIOLOGY

• For vertebrates, the sequence of nucleotides in telomeres is TTAGGG.

• Telomeres are repetitive nucleotide sequences located at the termini of linear chromosomes of most eukaryotic organisms.

• Most prokaryotes, lacking this linear arrangement, do not have telomeres.

• In most prokaryotes, chromosomes are circular and, thus, do not have ends to suffer premature replication termination.

HOW THEY HELP DURING DNA REPLICATION

HOW THEY HELP DURING DNA REPLICATION

HOW THEY HELP DURING DNA REPLICATION

HOW THEY HELP DURING DNA REPLICATION

TELOMERES SHORTEN DURING REPLICATION

• Before a cell can divide, it makes copies of its chromosomes so that both

new cells will have identical genetic material. To be copied, a

chromosome's two DNA strands must unwind and separate. An enzyme

(DNA polymerase) then reads the existing strands to build two new

strands. It begins the process with the help of short pieces of RNA. When

each new matching strand is complete, it is a bit shorter than the original

strand because of the room needed at the end for this small piece of

RNA. 

HOWEVER ,THERE IS TELOMERASE• Telomerase counteracts telomere shortening

• An enzyme named telomerase adds bases to the ends of telomeres. In

young cells, telomerase keeps telomeres from wearing down too much.

But as cells divide repeatedly, there is not enough telomerase, so the

telomeres grow shorter and the cells age.

• Telomerase remains active in sperm and eggs, which are passed from one

generation to the next. If reproductive cells did not have telomerase to

maintain the length of their telomeres, any organism with such cells

would soon go extinct.

Telomerase is a ribonucleoprotein enzyme complex (a cellular reverse transcriptase) that has been referred to as a cellular immortalizing enzyme.

It stabilizes telomere length by adding hexameric (TTAGGG) repeats onto the telomeric ends of the chromosomes, thus compensating for the erosion of telomeres that occurs in its absence.

TELOMERASE – MORE ABOUT IT

TELOMERES&

CANCER

• As a cell begins to become cancerous, it divides more often, and its telomeres become very short. If its telomeres get too short, the cell may die. Often times, these cells escape death by making more telomerase enzyme, which prevents the telomeres from getting even shorter.

• Many cancers have shortened telomeres, including pancreatic, bone, prostate, bladder, lung, kidney, head and neck.

• Measuring telomerase may be a way to detect cancer.

TELOMERES & CANCER• There is experimental

evidence from hundreds of independent laboratories that telomerase activity is present in almost all human tumors but not in tissues adjacent to the tumors.

• Thus, clinical telomerase research is currently focused on the development of methods for the accurate diagnosis of cancer and on novel anti-telomerase cancer therapeutics

TELOMERES & CANCER

NORMAL CELL AND CANCER CELL

Healthy human cells are mortal because they can divide only a finite number of times, growing older each time they divide. Thus cells in an elderly person are much older than cells in an infant.

Once the telomere shrinks to a certain level, the cell can no longer divide. Its metabolism slows down, it ages, and dies.

It has been proposed that telomere shortening is like a molecular clock mechanism that counts the number of times a cell has divided and when telomeres are short, cellular senescence (growth arrest) occurs.

According to research people older than 60 with shorter telomeres were 3 times more likely to die from heart disease and 8 times more likely to die from infectious disease. It also suggests that lifespan could be increased 5 years by increasing the length of telomeres in people with shorter ones.

TELOMERE & AGEING

Later on a study in mice suggested that premature ageing can be reversed by reactivating an enzyme that protects the tips of chromosomes i.e. Telomerase.

Dr. Jerry Shay and his colleagues (The University of Texas Southwestern Medical Center at Dallas ) found that cellular aging can be bypassed or put on hold by the introduction of the catalytic component of “Telomerase” .

REVERSING AGEING

In the laboratory, cells in tissue culture with

introduced telomerase have extended the length

of their telomeres. They have already divided for

250 generations past the time they normally would

stop dividing, and are continuing to divide

normally, giving rise to normal cells with the

normal number of chromosomes

Without telomerase

With telomerase

NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE 

Three US scientists have won the Nobel Prize in Physiology or Medicine for discovering the structure of molecular caps called telomeres and working out how they protect chromosomes from degradation.

The prize, announced on 5 October, is shared equally between Elizabeth Blackburn at the University of California, San Francisco, Carol Greider of the Johns Hopkins Medical School in Baltimore, Maryland, and Jack Szostak at Harvard Medical School in Boston, Massachusetts.

Winners : Carol Greider, Elizabeth Blackburn and Jack Szostak. (Left to right)

SCIENTISTS DISCOVER LINK BETWEEN AGEING PROCESS AND HORMONE RELEASED FROM MUSCLE AFTER

EXERCISE

• Published on February 18,2014

• The research team led by Dr James Brown have proven a significant link

exists between Irisin levels in the blood and a biological marker of

ageing called telomere length.

• Short telomere length has been linked to many age-related diseases

including cancer, heart disease and Alzheimer's disease.

• Individuals who had higher levels of Irisin were found to

have longer telomeres.

 MELANOMA RISK

A leading Dartmouth researcher, working with The Melanoma Genetics

Consortium, GenoMEL, an international research consortium, co-

authored a paper published on September 21,2014 in the Journal of

the National Cancer Institute that proves longer telomeres increase the

risk of melanoma.

"For the first time, we have established that the genes controlling the

length of these telomeres play a part in the risk of developing

melanoma," said lead author of the study Mark Iles, PhD, School of

Medicine at the University of Leeds (UK).

 MELANOMA RISK

• After research, one in four people predicted to have the longest telomeres are at 30

percent increased risk of developing melanoma compared to those one in four predicted

to have the shortest telomeres.

• The explanation for why a longer telomere is connected to melanoma is not yet known.

Researchers propose that having a longer telomere may delay a cellular aging process,

which increases the likelihood cellular variation.

• This research is important because it suggests that abnormal cell life span could play a

key role in the development of melanomas!!

BIBLIOGRAPHY• Longer telomeres increase melanoma risk

Published on September 21, 2014 at 1:17 PM

http://www.news-medical.net/news/20140921/Longer-telomeres-increase-melanoma-risk.aspx

• Telomerase reverses ageing process

Published online 28 November 2010

http://www.nature.com/news/2010/101128/full/news.2010.635.html

• Prize for physiology or medicine awarded for uncovering role of telomeres.

Published online 5 October 2009

http://www.nature.com/news/2009/091005/full/461706a.html

•  Scientists discover link between ageing process and hormone released from muscle after exercise

Published on February 18, 2014

http://www.news-medical.net/news/20140218/Scientists-discover-link-between-ageing-process-and-hormone-released-from-muscle-after-exercise.aspx

BIBLIOGRAPHY

• http://en.wikipedia.org/wiki/Telomere

• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Telomeres.html

Presented By: Group IRicha Verma

Swapnil KhilariwalVaibhaw Hirawat

THANK YOU

QUESTIONS PLEASE