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A Review Article by Rune Toftgard, Member of the Nobel
Assembly ( http://nobelprize.org) about the research that
was awarded by 2009 Nobel prize in Medicine & Physiology:
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Genetics, A Conceptual Approach
By Benjamin A. Pierce,
The 4th edition © 2012
ISBN-13: 978-1-4292-3250-0
ISBN-10: 1-4292-3250-1
Concepts of Genetics
By William S. Klug,
The 10th edition © 2012
ISBN-13: 978-0-321-72412-0 (student ed.)
ISBN-10: 0-321-72412-7 (student ed.)
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1- Title & References
2- Introduction
3- Telomere Structure & Functions
4- Telomere Throughout the Evolution
5- A Quick glance to Linear DNA Replication
6- End Replication Problem
7- Telomerase Structure
8- Telomerase Bio-Activity
9- Conclusions
10- Telomerase, the Key to Immortality?!
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Since 1962 , 22 Nobel prizes have been awarded to the
researches of Genetics & Genomics and the last one was
devoted in 2009
2009 Nobel prize in Medicine & Physiology was awarded for
the discovery of how chromosomes are protected by Telomeres
and the enzyme Telomerase
(Elizabeth H blackburn , Carol W. Greider & Jack W. Szostak)
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Telomeres are the natural ends of a chromosome
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Pioneering work by Hermann Muller (on fruit flies) and Barbara
McClintock (on corn) showed that chromosome breaks produce unstable
ends that have a tendency to stick together and enable the chromosome to
be degraded.
- Because attachment and degradation do not happen to the ends of a
chromosome that has telomeres, each telomere must serve as a cap that
stabilizes the chromosome, much as the plastic tips on the ends of a shoelace
prevent the lace from unraveling.
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First discovered by Elizabeth Blackburn and Joe Gall in their study of
Micronuclei in the ciliated protozoan Tetrahymena—the DNA at the
protozoan’s chromosome ends consists of the short tandem repeating
sequence TTGGGG (G-Rich Strand). In a similar way, all vertebrates
contain the sequence TTAGGG
This is 12-16 Nucleotides long in Tetrahymena and several hundredBut
How this tandemly repeated DNA confers inertness to the chromosome
ends?!
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Telomeric DNA sequences have been highly conserved throughout
evolution, reflecting the critical function of telomeres.
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1- Each time a cell divides, an average person loses 30 to 200 base pairs from
the ends of that cell's telomeres
2- Cells normally can divide only about 50 to 70 times, with telomeres
getting progressively shorter until the cells become senescent, die or sustain
genetic damage that can cause cancer.
Example: In human blood cells, the length of telomeres ranges from 8,000
base pairs at birth to 3,000 base pairs as people age and as low as 1,500 in
elderly people
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Telomerase is a unique ribonucleoprotein complex whose principal role
is the maintenance of telomeres, the heterochromatic structures made of
G-rich repeated sequences
Human telomerase is composed of two main subunits: the human
telomerase RNA (TR), which harbors an 11 nucleotide long sequence (in
human) acting as a template for synthesis of telomeric repeats, and the
telomerase reverse transcriptase (TERT), which is the core catalytic
subunit of the enzyme.
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1 – Blackburn, Greider and Szostak solved a longstanding
fundamental problem in biology; how can the ends of chromosomes be
maintained and spared from erosion or rearrangement during repeated
cellular divisions? They opened a whole new research field related to
the all Life science
2- By ingenious genetic experiments they demonstrated that
chromosomal termini have an evolutionarily conserved structure and
function.
3- They have discovered how the conserved function of chromosomal
telomere repeat sequences protects against degradation and
recombination events and have identified a new enzyme complex,
telomerase.
4- Deficiency of telomerase results in a so called replicative senescence.
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5- most cancer cells maintain telomeres via increased telomerase
activity.
6- These Studies have provided very important insights into other areas
of high medical relevance such as: ageing and hereditary disease
syndromes although the connections are more complex than initially
anticipated.
7- The discoveries have also led to the development of new therapeutic
strategies for cancer treatment based on the targeting of telomerase
activity or expression that are now undergoing clinical testing. (such as
GRN163L drug that has had successful clinical trials)
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Thank you for your attention
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Genetics, A Conceptual Approach
By Benjamin A. Pierce,
The 4th edition © 2012
ISBN-13: 978-1-4292-3250-0
ISBN-10: 1-4292-3250-1
Concepts of Genetics
By William S. Klug,
The 10th edition © 2012
ISBN-13: 978-0-321-72412-0 (student ed.)
ISBN-10: 0-321-72412-7 (student ed.)
23
24
A Review Article by Rune Toftgard, Member of the Nobel
Assembly ( http://nobelprize.org) about the research that
was awarded by 2009 Nobel prize in Medicine & Physiology:
25