Diapositiva 1

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Dr. José María Romero Romero
TELOMERES
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TELOMERES
TELOMERES

• are specialized structures at the end of all
  eukaryotic chromosomes.

• ensure chromosome stability and protect the
  ends from degradation and from fusing with other
  chromosomes.

• contain longthy streches of non-coding tandemly
  repeated sequence, (TTAGGG)n, and specific
  proteins.

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TELOMERES

• Normal somatic cells lose telomeric repeats
  with ongoing cell division.

• Telomere length is quite important for cells
  because they work as a buffer avoiding the loss
  of coding DNA.

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TELOMERES

• The loss of telomeric repeats triggers
  replicative senescense in cells.

• Telomeres sequences are extraordinary highly
  conserved in evolution all vertebrates have the
  same simple sequence repeat.

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TELOMERES

• There is an important enzyme TELOMERASE,
  active only in embryonic, proliferatice cells of
  renewal tissues, adult male germline and cancer
  cells, that is the main regulator of telomeres
  length.

• TELOMERASE is a reverse transcriptase ( a
  RNA-dependent polymerase) that contains an RNA
  with the sequence complementary to the telomere
  repeat TTAGGG. RNAs polymerase is used as the
  template.

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TELOMERES

• The model for telomeres is that they are the
  physical ends of linear eukaryotic chromosomes
  that contain up to 15 Kb of non-coding tandemly
  repeated sequence (TTAGGG)n, and specific
  proteins, and an overhang of 50- 200 nucleotides
  in the chromosome terminus.

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TELOMERES
Model of a human telomere
DNA Chromosome
DNA tandem repeat - (TTAGGG)n
3
5
5-15kb
30-200 nt
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TELOMERES
T- LOOP
D-LOOP
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5
TTAGGGTTAGGGTTAGGGTTA
AATCCCAATCCCAA TCCCAAT
3
3overhang
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TELOMERES
3overhang erosion
This telomere structure hasnt stability
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5
TTAGGGTT
AATCCCAATCCCAA TCCCAAT
3
3overhang
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TELOMERES
3overhang erosion
5
3
Damaged chromosomes are degraded by nucleases and
participate in end joining reactions that fuse
two free ends.
Chromosomal destabilization is linked to
malignancies