DEPARTMENT OF MATHEMATICS AND NATURAL SCIENCES UNIVERSITY OF TURKU

Department of Mathematics and Natural Sciences, University of Turku

MOLECULAR BIOLOGY
TELOMERE AND RELATED ILLENESSES By: Arsalan Ali Shah

Department of Mathematics and Natural Sciences, University of Turku

Overview

TELOMERE AND RELATED ILLENESSES

Definition Structure Location Functions Telomerase Various diseases connected to telomere Areas of Research
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1. Introduction

2. Illnesses

Introduction
A telomere is a region of repetitive DNA sequences at the end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. derived from the Greek nouns telos () "end" and mers (, root: -) "part".

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Introduction Cont..

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Introduction>Structure
Telomeres are Repetitive DNA sequences at the ends of all human chromosomes They contain thousands of repeats of the six-nucleotide sequence, TTAGGG In humans there are 46 chromosomes and thus 92 telomeres (one at each end) folded back and protected by protein complexes known as 'shelterin' .
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Introduction>Structure

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Introduction>Functions
Telomeres are also thought to be the "clock" that regulates how many times a cell can divide. Decides Senescence. Regulatory Elements during Meosis. Are disposable. Divisions by Hayflicks limit.

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Introduction>functions cont..

(a) prevents a DNA-damage response (DDR) and chromosome end-to-end fusions through the combination of a structural conformation (such as a telomere loop (t-loop)) and the presence of sufficient shelterin proteins. An intermediate-state telomere

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Introduction>functions cont..

(b), for reasons that are essentially unknown (but might include relative undersaturation of the telomere with shelterin proteins), is able to prevent end-to-end fusions but not a DDR.. In the fully uncapped telomere state

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Introduction>functions cont..

(c), chromosome ends retain insufficient levels of shelterin to inhibit chromosome endto-end fusions.

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How are telomeres linked to aging?

Once the telomere shrinks to a certain level, the cell can no longer divide. Its metabolism slows down, it ages, and dies. It is believed that shortened telomeres in mitotic (dividing) cells may be responsible for some of the changes we associate with normal aging.
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Introduction>Telomerase
Telomerase (TEE-LM-ER-ACE) 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.
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Introduction>TelomeraseCont..

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Introduction>TelomeraseCont..
Telomerase works by adding back telomeric DNA to the ends of chromosomes, thus compensating for the loss of telomeres that normally occurs as cells divide. Most normal cells do not have this enzyme and thus they lose telomeres with each division.

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Introduction>TelomeraseCont..
Research also shows that the counter that controls the wasting away of the telomere can be "turned on" and "turned off". The control button appears to be an enzyme called telomerase which can rejuvenate the telomere and allow the cell to divide endlessly. Most cells of the body contain telomerase but it is in the "off" position so that the cell is mortal and eventually dies.
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Introduction>TelomeraseCont..
The next slide shows cells stained to visualize the presence of telomerase. The bottom dish was treated to produce active telomerase and is still dividing The top dish of normal cells of the same age has stopped dividing

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ILLNESSES

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Illnesses cont..

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Illnesses cont..
Aging Many experiments have shown that there is a direct relationship between telomeres and aging, and that telomerase has the ability to prolong life and cell division.

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Illnesses cont..

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Illnesses cont..
Genetic Instability Aplastic Anemia FSHD Tumors Cancer

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Illnesses cont..
FSHD (Faciocapulohumeral Muscular Dystrophy) 3rd most common muscular dystrophy Autosomal pattern of inheritance Contraction of polymorphic repeat array in the sub-telomere at 4q.

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Illnesses cont..

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Illnesses cont..

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Illnesses cont..

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Illnesses cont..
Aplastic Anemia Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells.

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Illnesses cont..
Cancer

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Illnesses cont..

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Sources
1. Reveal P J, Henkels K M, and Truchi J J. 1997 "Synthesis of the Mammalian Telomere Lagging Strand in Vitro." Journal Of BioChemistry Vol. 272:No. 18 pp1167811681 2. Scientific American Turning Back the Strands of Time 3. McElligott R, and Wellinger R J. 1997 "The Terminal DNA Structure of Mammalian Chromosomes." EMBO Journal Vol. 16:no. 12 pp 3705-3714. (www.emboj.org/)

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Sources
4. http://www.sciencedaily.com/releases/200 9/10/091005110401.htm 5. http://modexstaging.com/recharge/aging. php?page=30 6. http://en.wikipedia.org 7. http://www.suite101.com/view_image_art icles.cfm/2874349 8. Telomere Functions. A Review by E. V. Kurenova and J. M. Mason
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