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SCIENCE NEWS DIGEST FOR PHYSICIANS AND SCIENTISTS


Voir également Telomerase: End of Cancer ?
Voir également Télomérase: la confirmation (12/1998)

CELL BIOLOGY

TELOMERASE IN NORMAL CELLS

Telomeres are the ends of chromosomes and consist of short, tandemly repeated [(TTAGGG)n]> DNA sequences which are associated with various proteins.
Due to incomplete DNA replication, during S phase of each cell cylce, parts of these telomeres are lost.
It is thought that it is the function of telomerase is to counteract this loss.

Telomerase is a ribonucleoprotein which recognizes a single-stranded G-rich telomere primer and, by using an RNA template, adds multiple telomeric repeats to its 3' end.
Therefore, loss of telomeres is more severe is cells that do not have telomerase.
It is thought that tumor cells, by virtue of having adequate amount of telomerase activity are able to repair the segments of telomeres that are lost during their cell division.

Kim et al described in the Dec 1994 of Science a PCR-based methodology for measuring telomerase activity in tissues.
This technique greatly simplified detection of telomerase in tissues and opened the possibility to examine telomerase activity in various types of cells and under various experimental conditions.
Kim et al demonstrated that 90 of 101 biopsies of human tumors exhibited telomerase activity, whereas none of the 50 normal somatic tissues were found to be positive.

Although it is a widely held view that normal cells have lillte or no detectable telomerase activity, in the October 15 issue of Journal of Immunology, Hiyama et al described up-regulation of telomerase activity in normal human normal cells.
The telomerase activity was detectable at low levels in normal human T and B cells and increased by in vitro mitogenic stimulation, and by prolifertaion and differentation in the hematopoietic cells.
On the other hand, aging was associated with a decrease in the telomerase activity in these cells. In the June 11, 96 issue of Proceedings of National Academy of Sciences, Härle-Bachor, and Boukamp reported that the normal cells from human epidermis also exhibit telomerase activity.
>Therefore, telomerase seems to play a role in the biology of lymphoid cells and in the regenerative capacity of normal epidermis in vivo.

Telomeric repeat sequences in eukaryotes

Group Organism (d) Telomeric repeat (5' to 3' toward the end)
Vertebrates Human, mouse, Xenopus (b) TTAGGG
Filamentous fungi Neurospora TTAGGG
Slime molds Physarum, Didymium
Dictyostelium
TTAGGG
AG(1-8)
Kinetoplastid protozoa Trypanosoma, Crithidia TTAGGG
Ciliated protozoa Tetrahymena, Glaucoma
Paramecium
Oxytricha, Stylonychia, Euplotes
TTGGGG
TTGGG(T/G)
TTTTGGGG
Sporozoite protozoa Plasmodium TTAGGG(T/C)
Higher plants Arabidopsis TTTAGGG
Insects (c) Bombyx mori TTAGG
Nematodes Ascaris lumbricoides TTAGGC
Alga Chlamydomonas TTTTAGGG
Fission yeasts Schizosaccharomyces pombe TTAC(A)(C)G(1-8)
Budding yeasts Saccharomyces cerevisiae

Candida glabrata
Candida albicans
Candida tropicalis
Candida maltosa
Candida guillermondii
Candida pseudotropicalis
Kluyveromyces lactis
TGTGGGTGTGGTG (from RNA template) (e)
or G(2-3)(TG)(1-6)T (consensus)
GGGGTCTGGGTGCTG
GGTGTA C GGATGTCTAACTTCTT
GGTGTA(C/A)GGATGTCACGATCATT
GGTGTA C GGATGCAGACTCGCTT
GGTGTA C
GGTGTA C GGATTTGATTAGTTATGT
GGTGTA C GGATTTGATTAGGTATGT
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