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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.

REFERENCES:

Keiko Hiyama, Yuko Hirai, Seishi Kyoizumi, Mitoshi Akiyama, Eiso Hiyama, Mieczyslaw A. Piatyszek, Jerry W. Shay, Shinichi Ishioka, Michio Yamakido: Activation of telomerase in human lymphocytes and hematopoietic progenitor cells.The Journal of Immunology: 155, 3711 - 3715, 1995
Cosima Härle-Bachor, Petra Boukamp: Telomerase activity in the regenerative basal layer of the epidermis in human skin and in immortal and carcinoma-derived skin keratinocytes. Proc Natl Acad Sci USA 93, 6474-6481, 1996
Kim, 1994
Specific association of human telomerase activity with immortal cells and cancer.
Science 266, 2011-2015 (1994) [95099329]
(View Citation format,Abstract format,MEDLARS format,ASN.1 format,Save As..., or 30 MEDLINE neighbors)

Sites:

Telomere (GenoBase: EMBL Keyword Index)

Telomerase RNA
Telomere
Telomere associated repeat sequence
Telomere elongation
Telomere repeat
Telomere resolution
Telomere-associated proteins-binding
Telomere-binding protein
Telomere-binding protein alpha subunit alanine version
Telomere-binding protein alpha subunit serine version
Telomeric DNA
Telomeric repeat
Kluyveromyces lactis terlomerase RNA component (TER1) sequence

Yeast telomere related genes

TLC1 (sequence from Singer & Gottschling)

Cloned telomerase gene sequences

Telomerase RNAs

Euplotes aediculatus
Euplotes crassus
Euplotes eurystomus
Oxytricha nova
Oxytricha trifallax
Stylonychia lemnae
Stylonychia mytilis
Tetrahymena australis
Tetrahymena borealis
Tetrahymena capricornis
Tetrahymena paravorax
Tetrahymena silvana
Tetrahymena vorax
Kluyveromyces lactis
Saccharomyces cerevisiae(in chromosome XII)
Mus musculus
Homo sapiens

Telomerase Proteins

Tetrahymena thermophila [p80] [p95]
Database Links:

2 MEDLINE Citations [OMIM]

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

RESOURCES:

Telomerase and Cancer: Diagnostics, Prognostics and Therapeutic Implications
Telomere & Telomerase
Telomere (GenoBase : EMBL Keyword Index)
GenLink Multimedia Telomere Resource
The Life Extension Foundation
Cloned Telomerase Gene Sequences
Search the Telomere Literature Database
Telomere Researchers Directory
Mus musculus telomerase RNA component gene
hTR=RNA component of telomerase [human, 293 cells, Genomic, 962 nt]
Lists of NIH Funded Research Groups [Gopher Search]: Telomere
Lists of NIH Funded Research Groups [Gopher Search]: Telomerase

DATABASE LINKS:

46 MEDLINE Citations [OMIM]


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