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Telomere13
Telomeres
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Telomere
A telomere is a region of repetitive DNA at the end of a,
from deterioration.
ce s v e w ou e omeres, ey wou ose eends of their chromosomes, and the necessary informationthe contain.
The Nobel Prize in Physiology or Medicine 2009Elizabeth H. Blackburn, Carol W. Greider, Jack W. Szostak
"how chromosomes are protected bye omeres an e enzyme e omerase
Telomeres are the ends of chromosomes
Nucleotides
ruc ure
DNA
Adenine Guanine
NucleosomeHistones
DNA DoubleC tosineTh mine
Adenine always pairs withThymine by 2 hydrogen bonds,while Guanine pairs withMeta hase
Chromatin
Cytosine through 3 hydrogenbonds
chromosome
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Why telomeres is shorten during cell division
Sugar-phosphate
Sugar-phosphate
ruc ure
100 – 200million
backbone ac one
Base pair
ase pa r
10 trillion(10 )cells
Hydrogen bond
DNA Double
Fertilized egg (Zygote)
Telomere structuree omeres are repe ve sequences
located at the termini of linear chromosomesof most eukaryotic organisms
Group organism Telomeric repeat(5’ to 3’ toward the end)
Vertebrates Human TTAGGGMouse TTAGGGXenopus TTAGGG
TelomeresEmbr onic
Long
Telomere is aChromosome
stem cells
e r e s
sequenceAdult stemcells
T e
l o
Short
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Telomeres are made of simple DNA repeatsbound by specific proteins
’
Telomere DNA
5’T T A G G G
,regions are single strains.
For telomeres functions, proteins bound alongo DNA.
The end replication problem shortens telomeres
3’Telomere
5’
Replication
Telomeres are shorten in cells divisions
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Telomere length and Aged
15.000 base pair Fetus
10.000 base pair Born
. ase pa r Aged
Telomere shorten with in vitro cells culture & with age
Culture withtelomerase
Culture withouttelomerase
e omere s or en ur ng n v ro cu ure
Telomere shorten with age in people
14000
12000
10000
8000 B p
6000
4000
2000
020 40 60 80 100Telomere length
age
Telomere length
Telomeres shorten during ageing of human fibroblasts
Calvin B. Harley et al., Nature 2000
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Why did telomere get shorter?
Cell division
DNA replication
DNA replication
DNA replication
DNA stop replication Cell death
Telomere length in Germ cell and somatic cells
The common biology of cancer and ageing
Toren Finkel et al. Nature 2007
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How can we prevent telomere shortening?
Our Reproductive Cells
ge
Telomere Shortening DOES NOT
Occur in Our Reproductive Cells
Telomerase Lengthens Telomeres
3’ 3’
Telomerase
RNA template
RNA primer
DNA polymerase
Information of chromosomeis com leted new DNA
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How do we produce telomerase in all our cells
Our Simple Strategy
Somatic cells Do not produce telomeraseSomatic cells contain the gene for telomerase
The gene is shut OFF
l ’ rn i
Reproductive cells produce telomerase
Telomerase geneRegulatoryelement
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Telomeres in Cloned Animals
The first cloned animal, Dolly, was revealed to have shorttelomeres that were com arable to the a e of the cell donor
P.G. Shiels et al., Analysis of telomere lengths in cloned sheep, Nature 399 (1999).
Normal telomere len ths were found in cloned cattleX.C. Tian et al., Nat. Genet. 26 (2000)
Clones cloned over 5 generations did not have shorter
e omeres n m ce . a ayama, et a ., ature ( )
ese reports n cate t at te omere engt s
from the adult somatic cells can be reset bSCNT!!??
Telomerase in different cells types
The enzyme telomerase which elongates telomeres is activein germ cells and early embryonic development.
S. Schaetzlein et al. Telomere len th is reset durin earl mammalian. , .,
embryogenesis, Proc. Natl. Acad. Sci. U. S. A. 101 (21) (2004).
The telomere length of donor nuclei telomere elongation
and cattle Liu, S.M. et al., Telomere lengthening early in development, Nat. Cell Biol. 9 (12) (2007)
me y rans erases an s one me y rans erases
control telomere length in mammalian cells. , .,
telomere recombination in mammalian cells, Nat. Cell Biol. 8 (4) (2006)
resulted in significantly increase the full-term developmentof cloned animal.