Telomerase is an enzyme that adds telomere repeats, ("TTAGGG" in all vertebrates) to the 3' ("three prime") end of DNA strands. The enzyme is a reverse transcriptase that carries its own RNA template. By lengthening the strand before replication, cells with re-activated telomerase catalytic activity are able to compensate for telomere shortening during DNA replication of more than 86 population doublings (the Hayflick limit) and restore themselves from senescence, back into normal somatic cells again, that act and divide like normal young cells again. With the gene for telomerase enzyme added, normal human cells have now been living normally for 600 plus population doublings instead of 86. (Clontech's Infinity line of telomerase-immortalized cells). These cells look, act and divide vigorously, just like young cells do, with no signs of aging nor transformation, even after 600 plus divisions.
In humans, telomerase starts out as a gene called hTERT (Human Telomerase Reverse Transcriptase). Its gene is located very near the end of the bottom of chromosome 5 , and it is only expressed by haploid cells like sperm or ovum or very young somatic cells in infancy, stem cells and finally in special bone marrow cells that pass through the thymus gland and become initiated as thymic initiated cells (T-cells). And from these T-cells, our bodies receive a distributed small amount of telomerase, that peaks at adolescence and then begins to diminish in time, until the thymus gland all but disappears, along with the production of T-cells and thereby telomerase to the rest of our cells, until we have practically no more telomerase enzyme at the age of 45 years old, since there is no more thymus gland either.
Children born without the thymus gland (Progeriacs) or without the production of this enzyme (Werner syndrome) or people with trauma or diseases of the thymus gland, (Myasthenia gravis) begin to age, degrade and waste quickly, without a thymus and the production of telomerase via the thymus-initiated cells (T-cells) telomerase distribution system (the lymphatic system). From there it is expressed from its DNA form into nRNA (nuclear RNA) then its exons are spliced into mRNA (into a sequence of about 4,020 base pairs long) which then travel out of the nucleus through the nucleic pores out into the ribosomes, where it is decoded as a two-part ribonucleoprotein enzyme, which then binds with a piece of circular single stranded RNA (TP-1) telomerase-related Protein-1. The enzyme portion (hTERT) is made of folded proteins and the RNA template resembles mRNA. The RNA associates with hTERT and together bind to the 5' single stranded end of the chromosome. The RNA template aligns in place immediatelly following the last DNA base. Then a TTAGGG sequence is made and the whole telomerase/RNA complex slides forward exactly 6 base pairs. The process repeats itself.
External links
Last updated: 09-12-2005 02:39:13
