Telomerase Detection in Body Fluids‪.‬

The ends of chromosomes are stabilized and protected from degradation by intercellular nucleases by specialized nucleoprotein structures, the telomeres. The DNA component of telomeres consists of many hundreds to thousands of simple repeat sequences. In mammals, this sequence is 5'-TTAGGG-3' (1-3). Because the DNA replication machinery cannot fully replicate the ends of linear DNA, telomeres progressively shorten with each round of cell replication (4). Eventually, a critically short telomere length is reached, and the cell stops dividing and senesces (5-7). This phenomenon is thought to function as a type of "molecular clock", limiting the lifespan of individual cells. However, cell types that, as part of their normal biology, must replicate for many rounds of cell division, e.g., germ cells, embryonic cells, and stem cells, must posses a mechanism to "reset the clock" (8, 9). This mechanism is provided by the enzyme telomerase, a ribonucleoprotein that recognizes the ends of telomeres and adds additional repeats (1-3). In most postembryonic cell types, telomerase activity is down-regulated; in cancer cells, however, telomerase expression is activated (8-11). Therefore, telomerase has been the focus of much research over the past several years, with increasing interest in the role of this enzyme in carcinogenesis, as a target for anticancer chemotherapy, and as a biomarker for the detection of cancer. Telomerase is a ribonucleoprotein consisting of three components: two protein subunits and an RNA subunit. The catalytic core consists of hTERT, the catalytic subunit that possesses reverse transcriptase activity, and hTR, the coding RNA component (12-14). The second telomerase protein, hTP, may play a structural role. hTR and hTP are expressed ubiquitously, with hTERT expression being the rate-limiting step for telomerase activity (15).