| Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis using mouse models. | |
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MedLine Citation:
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PMID: 15860505 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Critical telomere shortening in the absence of telomerase in late generation Terc-/- mice (G3 Terc-/-) or loss of telomere capping due to abrogation of the DNA repair/telomere binding protein Ku86 (Ku86-/- mice) results in telomere dysfunction and organismal premature aging. Here, we report on genome-wide transcription in mouse G3 Terc-/-, Ku86-/- and G3 Terc-/-/Ku86-/- germ cells using high-density oligonucleotide microarrays. Although a few transcripts are modulated specifically in Ku86- or Terc-deficient cells, the observed transcriptional response is mainly inductive and qualitatively similar for all three genotypes, with highest transcriptional induction observed in double mutant G3 Terc-/-/Ku86-/- cells compared with either single mutant. Analysis of 92 known genes induced in G3 Terc-/-/Ku86-/- germ cells compared with wild-type cells shows predominance of genes involved in cell adhesion, cell-to-cell and cell-to-matrix communication, as well as increased metabolic turnover and augmented antioxidant responses. In addition, the data presented in this study support the view that telomere dysfunction induces a robust compensatory response to rescue impaired germ cell function through the induction of survival signals related to the PI3-kinase pathway, as well as by the coordinated upregulation of transcripts that are essential for mammalian spermatogenesis. |
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Authors:
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Sonia Franco; Andrés Canela; Peter Klatt; María A Blasco |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-04-28 |
Journal Detail:
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Title: Carcinogenesis Volume: 26 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-24 Completed Date: 2005-11-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 1613-26 Citation Subset: IM |
Affiliation:
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Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Center (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, Nuclear / genetics* DNA-Binding Proteins / deficiency, genetics* Gene Expression Regulation Mice Mice, Knockout Models, Animal Oligonucleotide Array Sequence Analysis Reference Values Telomerase / deficiency*, genetics, metabolism* Telomere / genetics* Transcription, Genetic* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ku autoantigen; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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