Télomère

History

As of the Thirties, the end of the chromosomes is suspectée to have a role in the protection of the latter.

The structure in sequences repeated of DNA was noted in the Seventies and Eighties. The télomérase is discovered during the same period and its role was apprehended by Elizabeth Blackburn, Carol Greider, and Szostak Jack. The importance of the télomères could be confirmed by the premature ageing of the clonée ewe Dolly

Structure and functions of the télomères

At the majority of the Procaryotic , the chromosomes are circular (Plasmide S), and thus do not have an end likely to be faded by an incomplete replication. A small proportion of the chromosomes Bacterium NS, (like those of Streptomyces and Borelia ), are in the shape of stick and have télomères of which the structure and the function differ notably from those from the chromosomes from the eucaryotes.

The télomères comprise repetitive sequences of DNA associated with various proteins, which ensure a protection of the chromosomal terminations. They prevent that the chromosome fringe and that its end is not regarded as a rupture of the double bit of DNA, which could lead to weldings of chromosomes by fusion of their télomère respective.

The Télomérase S, enzymes transcriptases specialized opposite, ensure the synthesis and the growth of the télomères, at the man and the majority of the other organizations.

Thus, in much of cellular types human, the replication of the DNA and the form of gene TERT, coding the opposite télomérase transcriptase, are repressed, the télomères these cells are thus shortened gradually with each division: it is said that they constitute biological clocks.

On the contrary, in fabrics with intense cellular multiplication, like the cell-stocks or the white globules of blood, gene TERT is expressed and the length of the télomères remains constant.

At the man, the repetitive sequence of the télomères is TTAGGG, over a length from 3 to 20 Kilobase S. From 100 to 300 additional kilobases of repetition connect the télomère to the remainder of the chromosome. These repetitions vary from one species to another but comprise many bases Guanine - Cytosine.

Télomères and ageing

At the majority of the multicellular eucaryotes, the télomérases are active only in the germinal Cellule S. Certaines theories explain why the progressive shortening of the télomères somatic cells would prove to be a possible cause of the Sénescence and would prevent the Cancer.

When the télomère becomes too short, he does not play any more his protective part. The cell will interpret this like a corruption of its DNA, will enter in senescence and will stop its growth. Such télomères too shortened can also cause a fusion of two chromosomes. As such deteriorations are not reparable in the ordinary somatic cells, they can cause a Apoptose cell.

Several diseases of the ageing, (whose Progeria, characterized by a very early ageing) are caused by an excessive shortening telomeric. The bodies worsen more especially as their constitutive cells die or enter in senescence.

A more important shortening of the télomères would be a marker of disease risk of coronary the at the man of Middle Age.

Télomères and cancer

The majority of cancers produce télomérase, but often with a late stage, carcinogenesis begin with an important erosion from the télomères.

The inhibition of the télomérase is a promising way for the treatment of certain cancers.

Changes of the télomérase

These changes are noted in certain diseases. It is the case of the congenital Dyskératose associating a central Anémie (by absence of formation of red globules in marrow), of the anomalies on the level of the mucous membranes of the mouth, the nails and the skin.

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