Dyskeratosis Congenita and Cancer in Mice Deficient in Ribosomal RNA Modification
- 10 January 2003
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 299 (5604) , 259-262
- https://doi.org/10.1126/science.1079447
Abstract
Mutations in DKC1 cause dyskeratosis congenita (DC), a disease characterized by premature aging and increased tumor susceptibility. The DKC1 protein binds to the box H + ACA small nucleolar RNAs and the RNA component of telomerase. Here we show that hypomorphic Dkc1 mutant ( Dkc1 m ) mice recapitulate in the first and second generations (G1 and G2) the clinical features of DC. Dkc1 m cells from G1 and G2 mice were impaired in ribosomal RNA pseudouridylation before the onset of disease. Reductions of telomere length in Dkc1 m mice became evident only in later generations. These results suggest that deregulated ribosome function is important in the initiation of DC, whereas telomere shortening may modify and/or exacerbate DC.Keywords
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