Dissecting dyskerin

The DKC1 gene encodes dyskerin, a pseudouridine synthase that binds to box H + ACA small nucleolar RNAs and to the RNA component of telomerase. DKC1 mutations cause dyskeratosis congenital, a rare recessive disease characterized by premature aging and cancer susceptibility. In the January 10 Science, Ruggero et al. describe analysis of a hypomorphic Dkc1 mutant mouse that manifests features of the human disease (Science 2003, 299:259-262). The mice have a two- to four-fold reduction in Dkc1 expression. By six months of age, over half the mice developed dyskeratosis syndrome symptoms, such as severe anemia, lymphopenia, dyskeratosis of the skin, and bone marrow failure. The animals were also highly prone to tumors, especially of the lung and mammary gland. After four generations, mutant mice began to show loss of telomeric repeats and of telomerase activity. The Dkc1 hypomorph provides a useful model of the human disease and demonstrates the importance of its role in rRNA modification.