Telomeres, telomerase and chromosome stability.

Telomeres in most species consist of repeat units of a small number of nucleotides that together with secondary structures and associated proteins stabilize the linear chromosomal DNA molecule. Chromosomes lose a small amount of telomeric DNA after each cell replication. It has been proposed that when telomeres shorten below a critical length, a DNA damage response pathway is activated and induces cell cycle arrest. In cells such as stem cells that maintain a proliferative capacity, telomere length is maintained by the reverse transcriptase, telomerase. In addition, telomerase activity is present in 90% of primary human tumors, suggesting a role for telomerase in providing a proliferative capacity to cells, which is a requirement in progression to malignancy. Telomerase activity can be involved in chromosome healing, although telomerase-independent processes also appear to be capable of capping broken chromosome ends. This review describes the structure and maintenance of telomeres, the importance of a critical telomere length to cell proliferation and the telomeric status of broken chromosome ends produced during development or by spontaneous or induced DNA damages.