Dyskeratosis congenita (DKC) is a rare inherited disorder that is characterized by early death from bone marrow failure or pulmonary complications (1). Other symptoms include fragile bones, the absence of hair, progressive nail dystrophy, darkening or absence of skin color, underdeveloped testes, precancerous cells in mucous membranes, abnormalities of the gastrointestinal tract, pulmonary fibrosis, and an increased risk of skin cancer (1). The defect is caused by mutations in the DKC1 gene that encodes the protein dyskerin. This protein resembles the yeast protein Cbf5p, believed to be involved in the production of ribosomal RNA (rRNA)(2). In a recent issue of Nature, Collins and colleagues (3) now demonstrate that DKC may not be caused by a deficiency in rRNA, but rather by a defect in the maintenance of telomeres (the repeat DNA sequences at the ends of chromosomes).

The enzyme telomerase is responsible for adding DNA sequences to the ends of chromosomes, replacing the terminal repeats lost during replication. Telomerase, a cellular reverse transcriptase, is a ribonucleoprotein (RNP) composed of both RNA and protein components (see the figure). It adds TTAGGG repeats to the ends of telomeres by copying a template within its own RNA (4). Telomerase activity is present in the cells of the early mammalian embryo, in germ line cells, in certain proliferating stem cells (such as those of the hematopoietic system), and in almost all cancer cells. Most normal cells have little or no telomerase activity and show progressive shortening of telomeres throughout their life-span, resulting in a limited proliferative capacity and eventual growth arrest. Introduction of the catalytic component of telomerase into these cells results in telomere maintenance and the bypass of growth arrest (5). There is much interest in understanding the regulation of telomere length, the identification of telomere-binding proteins, and the elucidation of the functions of the different telomerase components.