Telomerase

Telomeres, the repetitive, structured regions of DNA at the end of chromosomes, are required elements for chromosome integrity. These regions are not synthesized by the normal replicative DNA polymerases, but they are instead added to the end of chromosomal DNA by the telomerase ribonuclear protein, composed of an RNA template and the telomerase reverse transcriptase (TERT) protein.1 The telomeres form a unique structure that allows for linear DNA chromosomes to persist without the activation of DNA damage pathways. After expression of telomerase ceases during the differentiation of a cell, subsequent DNA replications cause a progressive shortening of telomeric regions of DNA as a result of the inability of normal replicative DNA polymerases to completely copy the end of chromosomes. Over time, the loss of telomeric DNA to the "end replication problem" results in the activation of a checkpoint similar to DNA damage responses.1,12 In normal cells, this telomeric checkpoint activation results in senescence, but mutations in the pRb pathway and the p53 pathway can allow these cells to continue to cycle.1,12 Although these cells can escape senescence, the shortening of telomeres continues with each replication, reducing overall telomere length to a critical level. At this crisis point, telomeres fail to protect chromosome ends, activating DNA damage responses that result in chromosome fusion, leading to breakage, genomic instability, and massive amounts of cell death.12 Rare escape mutants of crisis either reactivate telomerase to maintain telomere length or acquire mutations that activate the alternative lengthening of telomeres (ALT) pathway. For cancer cells to gain infinite replica-tive capacity, they must maintain telomere length via one of these two methods, most commonly reactivation of telom-erase expression.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

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