Telomerase

An enzyme (a biologic catalyst) that has to do with the telomere, the end of the chromosome which is composed of short repeated DNA sequences. Telomerase may play a role in the formation, maintenance, and renovation of telomeres and perhaps in such key processes as aging and cancer. On the DNA level, the telomere is a dull stretch of road. It is a length of DNA monotonously made up of a recurring motif of 6 nucleotide bases (namely, the sequence TTAGGG) together with various associated proteins. The TTAGGG motif is tandemly repeated; it reads TTAGGGTTAGGG and so on. Small amounts of these terminal TTAGGG sequences are lost from the tips of the chromosomes, but the addition of TTAGGG repeats by the enzyme telomerase compensates for this loss. Many human cells progressively lose terminal sequences from their chromosomes during the process of cell division, a loss that correlates with the apparent absence of telomerase in these cells. There has been considerable interest in a possible relationship between human telomeres on the one hand and cellular senescence and cellular immortality on the other. This interest pertains firstly to the question of a role for telomerase in aging and the corresponding question of the use of agents that inhibit telomerase as fountain-of- youth drugs. The interest in telomerase also includes the question of a role for telomerase in the malignant process and the question of the use of agents that inhibit telomerase as a new class of anti- tumor drugs. (In biochemical terms, telomerase acts as a telomerase-reverse transcriptase (TERT); it reverses the usual course of nucleic acid events (from DNA to RNA) and goes from RNA to DNA; it transcribes the RNA into DNA and so is a reverse-transcribing enzyme specific to the telomeric sequence. Telomerase is itself a ribonucleoprotein (a complex of RNA and protein). It has two unique features: it is able to recognize a single-stranded (G-rich) telomere primer and it is able to add multiple telomeric repeats to its end by using an RNA template.) A gene coding for telomerase has been located and "mapped" to chromosome subband 5p15.33.

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A reverse transcriptase comprising an RNA template, which acts as a die for the TTAGGG sequence, and a catalytic protein component that is not found in normal, aging somatic cells. T. mediates the repair or preservation of telomere regions (terminal sequences) of chromosomes.The aging process that takes place in normal somatic cells, and the natural limit on the number of times such cells can undergo mitosis, involves a sequential shortening of telomeres due to failure of terminal sequences to be replicated during mitosis. Cells in which this shortening does not occur (cancer cells, germ cells, hematopoietic stem cells, and others) display a transient expression of t., which not only delays the erosion of telomeres but actually adds DNA bases to telomeres. Experimental transfection of a gene for the catalytic component of t. into normal, aging cells results in extension of telomeres. Restoring telomere length appears to reset gene expression, cell morphology, and the replicative life span. It has therefore been suggested that such procedures may permit therapeutic modification of the cellular mechanisms underlying age-related diseases such as atherosclerosis, osteoarthritis, macular degeneration, and Alzheimer dementia. Cellular aging is but one element of clinical aging, however, others being heredity and environment. Although t. expression is an important marker of malignancy, it is not itself the cause of cancer. T. expression and telomere lengthening apparently do not alter normal cell cycle control, chromosome complement, or cell morphology.

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tel·o·me·rase te-'lō-mə-.rās, -.rāz n a DNA polymerase that is a ribonucleoprotein catalyzing the elongation of chromosomal telomeres in eukaryotic cell division and is particularly active in cancer cells

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telo·mer·ase (tə-loґmər-ās) a specialized RNA-directed DNA polymerase [EC 2.7.7.49] involved in the formation of telomeres, using RNA of the enzyme as a template to synthesize the tandem repeating DNA sequences that are added to the 3′ protruding ends of the telomeres, and also in maintaining telomere sequences during replication.