TELOMERE AND TELOMERASE Essay Research Paper An

TELOMERE AND TELOMERASE Essay, Research Paper

An Introduction To Telomere and Telomerase

The telomere-telomerase hypothesis of aging and cancer is based on the findings that most human tumors have telomerase activity while normal human somatic cells do not.

An emerging hypothesis is that the up regulation or reexpression of telomerase is a critical event responsible for continuous tumor cell growth. In contrast to normal cells, tumor cells show no loss of average telomere length with cell division. Through this suggestion immortalization may occur through a mutation of gene in the telomerase repression pathway allowing the expression of telomerase in cancer cells.

Telomerase is a ribonucleoprotein enzyme which stabilizes telomer length by adding hexametric(TTAGGG) repeats to telomeric ends of the chromosomes, thus compensating for the continued erosion of telomeres that occurs in its absence. Telomerase is normally only in cells that give rise to sperm and egg or in some stem cell lines, it maintains the integrity of the chromosomes. the sex cells are the only part of the body that are biologically required to be immortal, because if there was a progressive loss of chromosomes with each generation then this would lead to extinction. However when cells become cancerous, the enzyme telomerase is activated, this enables the cancerous cells to replicate without a limit and this process makes the cells immortal.

According to a research done by a team of researchers at the University of Texas,

An evaluation of cell lines from 18 different human tissues revealed the presence of telomerase in 98 of the 100 immortal cell lines, telomerase was not found in any of the 22 mortal cell lines.

Telomeres is a repeated DNA sequence(TTAGGG) found at the ends of linear chromosomes that protect the ends of the chromosome from degradation, or telomere can be defined as DNA sequences found at the ends of eukaryotic chromosomes which maintain the fidelity of genetic information during replication. At birth as determined by terminal restriction fragment analysis, telomeres consist of about 15,000 base pairs of repeated TTAGGG DNA sequences, which become shorter with each cell division owing to the end replication problem. Every time a cell divides it loses 25-200 DNA base pairs off the telomere ends. once this pruning has occurred about 100 times a cell ages and does not continue to divide. It has been proposed that telomere shortening may be a molecular clock that count the number of times a cell has divided and determines when cellular senescence occurs (cellular senescence is the limited capacity of cells to divide beyond a finite number of population doubling. In a lay man.s understanding this means cellular death. Normal diploid human cells have limited capacity to proliferate (are mortal).

There appear to be two mechanisms responsible for the proliferative failure of normal cells. The first, mortality stage 1, occurs when there are still at least several thousand base pairs of telomeric sequence left at the end of most of the chromosomes. It is possible that mortality stage 1 may be induced by the activation of genes located in the immediately

subtelomeric region of the chromosomes.

The second is the mortality stage 2 which represent the physiological result of critically short telomeres when cells are no longer able to protect the ends of the chromosomes, so that the end degradation and end to end fusion occurs and causes genomic instability and cell death).

While researching on a topic like this, couple of important questions came to mind, so I made effort to research and address some of these questions which might be considered important.

One of such questions is why do telomeres shorten.

the mechanism of DNA replication is different in linear chromosomes is different for each of the two strands, known as leading and lagging strands. the lagging strand is made as series of discrete fragment, each one requiring a new RNA primer to initiate synthesis. the DNA between the last RNA priming event and end of the chromosome cannot be filled in. {this process is known as the end replication problem} since a strand cannot copy its end, telomeres shortening is required to occur during progressive cell divisions. the shortened telomeres are inherited by daughter cells and process repeats itself again.

The mind may inquire if stopping the shortening of telomeres whether that will prevent the body parts from aging; according to researchers, slowing down the rate of telomere shortening might help reduce the extent at which the body ages. An experiment done by a group of researchers from the University of Texas helps clarify this statement in full, hybrids between immortal cells that express telomerase, and normal cells that lack telomerase, creates a cell with limited lifespan. Also experiments show that treatment of immortal human cell lines with oligonucleotide will resulted in telomere elongation.

Using this finding, the researchers tested the hypothesis that elongation of telomeres could extend the lifespan of a cell, this was done by treating an immortal human cell line with oligonucleotides to lengthen its telomere, and then fusing the cell to a mortal cell. this experiment showed that the hybrid cells had a longer lifespan, than the hybrids without elongated telomeres.