LIFESCI 3A03 Study Guide - Midterm Guide: Xeroderma Pigmentosum, Organ Transplantation, Fluorophore

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4 Feb 2013
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Telomere erosion & Aging theory
Ku proteins repair Double Strand breaks which occur 10 times a day in our cells. Since the ends of
chromosomes without telomeres resemble DNA damage, these Ku proteins tend to merge DNA strands
together which can lead to mutations in the genome.
Telomeres are protein complexes that are at the end of DNA strands, which protect the DNA from the Ku proteins
and prevent the loss of coding genes during DNA replication
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Duplex Telomeric DNA: consists of 4 to 15 kilobases which caps the end of chromosomes
1.
Single Stranded Telomeric DNA: consist of ~250 base pairs that have a 3' G-rich overhang
2.
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This explains why females live 15% longer than males
Telomeres shorten as we age, in males they start off with longer telomeres, that erode at a much higher rates
than females.
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To visualize telomeres we can use FISH. In this experiment we attach a complimentary DNA probe that is
covalently bonded to fluorophore, denature the sample and wait for hybridization. After DNA repair we can see
the telomeres under an fluorescent microscope
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What are Telomeres?
Telomeres are attached to the DNA strands via the sheltrin protein
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A T-loop is formed when the duplex telomeric DNA loops back and single stranded telomeric DNA invades
the duplex telomeric DNA, forming a protective "cap"
Sheltrin protein consists of 6 protein complexes and promote the formation of T-loops
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T-loops can malfunction when there is mutation in the sheltrin protein or a malfunction during DNA replication,
resulting in short telomeres
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Due to this the cells are no longer being renewed which results in increased risk of heart disease, liver
failure, Alzheimer's and diabetes
When the telomere is "critically" short it cannot form a T-loop, so p53 tumor suppressor is activated which signals
cellular senescence (The cell no longer divides, and doesn't die)
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Sheltrin
This is called "telomeric erosion"
Telomeres shorten after each DNA replication because the lagging strand has a RNA primer that cannot be
replaced by the replication machinery due to a lack of a 3' end (DNA POL 3 can only work with 3' ends)
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This results in the said critically short telomeres
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DNA replication problem
How do Adult Stem Cells and Cancer Cells overcome the DNA replication problem, since they are able to
proliferate indefinitely?
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Using an enzyme called telomerase which contains an RNA template of the telomere, using this template this
enzyme creates a DNA copy of the lose telomere which counters telomeric erosion
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The telomerase lengthens the 3' over hang which is then filled by okazaki fragments, resulting in the telomere
being synthesized during DNA replication
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Telomerase
A study done in mice show that activating telomerase with the mTERT gene increases life expectancy and slows
down telomeric erosion
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TA-65 which was extracted from a herb (A. Membranaceous), shows signs of telomerase activation in cells that
previously didn't have this expression
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Can telomerase activity result in longevity?
Adult stem cells and Aging theory
Adult stem cells are undifferentiated, limited cells that are present in the human body
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When they divide they give rise to another adult stem cells (renewing the old one) and a needed somatic cell to
replenish dying and aging cells
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Adults stem cells have telomeric erosion, despite the fact that they have telomerase activated in them, but they
age much slower than somatic cells
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What are adult stem cells?
Module 1 Midterm Review
January-31-13
12:36 AM
LIFE SCI 3A03 Page 1
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