Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification Journal Article

  


Authors: Ruggero, D.; Grisendi, S.; Piazza, F.; Rego, E.; Mari, F.; Rao, P. H.; Cordon-Cardo, C.; Pandolfi, P. P.
Article Title: Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification
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 (Dkc1m) mice recapitulate in the first and second generations (G1 and G2) the clinical features of DC. Dkc1m cells from G1 and G2 mice were impaired in ribosomal RNA pseudouridylation before the onset of disease. Reductions of telomere length in Dkc1m 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: controlled study; gene mutation; mutation; clinical feature; nonhuman; protein function; neoplasms; proteins; mouse; telomere; animals; cell cycle proteins; mice; bone marrow cells; in situ hybridization, fluorescence; cancer susceptibility; genetic predisposition to disease; apoptosis; genes; anemia; animal experiment; animal model; protein binding; telomerase; animalia; nuclear proteins; rna; tumors; hematopoietic stem cells; aging; ribosome rna; small nucleolar rna; rna, ribosomal; disease models, animal; colony-forming units assay; onset age; disease exacerbation; mutagenesis; diseases; protein modification; ribosomes; dyskeratosis congenita; pseudouridine; telomeres; cancer; male; female; priority journal; article
Journal Title: Science
Volume: 299
Issue: 5604
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2003-01-10
Start Page: 259
End Page: 262
Language: English
DOI: 10.1126/science.1079447
PUBMED: 12522253
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0037428129&partnerID=40&md5=414fe770f20c92172a758c8a1e209268
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Silvia Grisendi
    15 Grisendi
  2. Francesco Piazza
    13 Piazza
  3. Davide Ruggero
    13 Ruggero
  4. Pier Paolo Pandolfi Derinaldis
    353 Pandolfi Derinaldis
  5. Carlos Cordon-Cardo
    612 Cordon-Cardo
  6. Eduardo Rego
    18 Rego
  7. Francesca Mari
    2 Mari
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