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TELOMERES

Dr. José María Romero Romero. TELOMERES. 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.

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TELOMERES

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  1. Dr. José María Romero Romero TELOMERES

  2. 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.

  3. 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.

  4. 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.

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

  6. 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.

  7. TELOMERES Old model of a human telomere DNA Chromosome DNA tandem repeat - (TTAGGG)n 3’ 5’ 30-200 nt (3´overhang) 5-15kb

  8. TELOMERES New model of a human telomere T- LOOP D-LOOP 5´ 5´ TTAGGGTTAGGGTTAGGGTTA 3´ AATCCCAATCCCAA TCCCAAT 3´overhang,•200 nt

  9. TELOMERES During senescense most overhang drop below 100 nt, potencially disrupting the T-loop or another telomeric structure. This telomere structure hasn´t stability D-LOOP 5´ 5´ TTAGGGTT 3´ AATCCCAATCCCAA TCCCAAT 3´overhang, •100 nt

  10. TELOMERES 3´overhang erosion seems to be a direct result of continued cellular division and not of the senescense program itself, so when there are about 100 nt ... 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

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