Course: SAT 170 Introductory Biotechnology

Unit 3 Reading and Multimedia Assignment

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Telomere Replication

Telomeres protect the ends of DNA from natural cellular erosion and are shortened during each successive round of replication.

The DNA molecules in eukaryotic chromosomes are linear, having two ends. This is in contrast to bacterial chromosomes such as that in E. coli, which is a closed circle. While replicating the DNA, the eukaryotic DNA replication enzymes (the DNA polymerase protein complex) cannot replicate the sequences present at the ends of the chromosomes, or more precisely, the chromatid fibers Hence, these sequences and the information they carry may get lost.

Eukaryotic chromosomes have telomeres that help deal with this problem. A telomere is a region of repetitive DNA sequences at the end of a chromosome, which protect the end of the chromosome from deterioration or from fusion with neighboring chromosomes. The telomeres of humans consist of 100-1000 repeats (and in a few cases as many as 2000 repeats) of the sequence 5' TTAGGG 3'.

Telomeres are crucial to the life of the cell. They keep the ends of the various chromosomes in the cell from accidentally becoming attached to each other. The telomere regions also deter the degradation of genes near the ends of chromosomes by allowing for the shortening of chromosome ends, which occurs during chromosome replication. It is estimated that human telomeres lose about 100 base pairs from their telomeric DNA at each mitosis. Telomeres cap the end sequences and get lost in the process of DNA replication. If cells divided without telomeres, they would lose the ends of their chromosomes, and the necessary information they contain. The telomeres are disposable buffers blocking the ends of the chromosomes and are consumed during cell division.

Cells have an enzyme called telomerase which carries out the task of adding repetitive nucleotide sequences to the ends of the DNA. Telomerase thus replenishes the telomere cap of the DNA. In most multicellular eukaryotic organisms, telomerase is active only in germ cells, stem cells, and certain white blood cells. There are theories that suggest that the steady shortening of telomeres with each replication in somatic (body) cells may have a role in senescence and in the prevention of cancer. This is because the telomeres act as a sort of time-delay fuse. They eventually run out after a certain number of cell divisions and this results in the eventual loss of vital genetic information from the cell's chromosome with future divisions.

Most cancers arise from somatic cells. One of the crucial features that distinguishes a cancer cell from a normal somatic cell is its ability to divide indefinitely. It turns out that most (85–90%) cancer cells have regained the ability to synthesize high levels of telomerase throughout the cell cycle, and thus are able to prevent further shortening of their telomeres. Perhaps agents that prevent the expression of the gene for telomerase, or prevent the action of the enzyme, will provide a new class of weapons in the fight against cancer. But if telomerase activity, however brief, is essential for all cells, and if lack of telomerase hastens replicative senescence, it may also hasten the aging of the tissues that depend on newly-formed cells for continued health. This may be a trade off that is not worth making.