HAT accounts for the ability of cancer cells to proliferate in a manner that is out of control, whereas normal cells die after 40 to 60 cycles of replication? One mechanism that leads to the death of a normal cell is erosion of the structure that caps the ends of chromosomes—the telomere (from the Greek telos, meaning end, and meros, a component)—each time a cell divides. The clinical relevance of telomeres is that a cancer cell, unlike a normal cell, can repair eroded telomeres. The existence of this repair mechanism suggests a novel target for cancer treatment.

Before any cell can divide, it must first replicate the double-stranded DNA in its chromosomes. But the cell has a problem replicating the DNA at the telomeres, where there are over 1000 short base sequences, TTAGGG, repeated over and over again and a variety of DNA-binding proteins. In a normal cell, the replication machinery cannot copy the last few bases of the telomeres on one of the strands of DNA in the chromosome. As a result, the telomeres shorten with each round of DNA replication. The telomere, a kind of molecular cap, protects the ends of the chromosome against degradation and prevents ligation of the ends of DNA by DNA-repair enzymes. These functions are crucial to the cell. When repeated during many cell cycles, the wearing away of the telomere with each cell division eventually abrogates its protective function. As a result, the chromosomes become unstable, fused, or lost. Cells with such defects not only are unable to divide, but also may not survive; they may die as a result of apoptosis. Attrition of the telomere thereby limits the life span of many kinds of cells. There are, however, two distinctive kinds of cells—germ cells and early embryonic cells—that must overcome this problem, because the body cannot afford to lose them. They solve the problem of the truncated telomere by means of a complex of proteins and RNA called telomerase. The RNA component of this complex contains a template sequence on which the TTAGGG repeats at the ends of DNA can be synthesized.