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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.