Telomerase assay in renal cancer

Telomeres are repeating sequences located at each end of eukaryotic chromosomes. These sequences function to protect chromosome positioning and replication (1-3). In vertebrates, telomere DNA consists of tandem repeats of TTAGGG, 10-15 kb pairs long (4). In most normal cells, DNA replication during mitosis results in the loss of telomere sequences 50-100 bp at the 5' ends of DNA termini (1,5). This sequence loss is mandated by the end-replication-splicing problem (Fig. 1). Thus, telomeres progressively shorten with age in somatic cells in culture and in vivo. In contrast, cancer cells and malignant cell lines retain telomere length despite repeated mitosis (6). This is believed to be an essential component of immortalization for most cells. Fig. 1. End-replication problem. As the replication fork proceeds from left to right, the leading strand proceeds to replicate one strand of original DNA (see B). The direction of the lagging strand is opposite to the direction of the replication fork and relies on the ligation of Okazaki fragments, which are primed with short stretches. Most RNA primer is never replaced with DNA (see C). Consequently, each round of replication produced a daughter chromosome. These are deficient in the sequences corresponding to the original 3' ends.