| An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres. | |
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MedLine Citation:
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PMID: 16000404 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Telomerase deficiency leads to a progressive loss of telomeric DNA that eventually triggers cell apoptosis in human primary cells during prolonged growth in culture. Rare survivors can maintain telomere length through either activation of telomerase or recombination-based telomere lengthening, and thus proliferate indefinitely. We have explored the possibility that telomeres may be maintained through telomere sister chromatid exchange (T-SCE) in murine telomere reverse transcriptase-deficient (mTert-/-) splenocytes and ES cells. Because telomerase deficiency leads to gradual loss of telomeric DNA in mTert-/- splenocytes and ES cells and eventually to chromosomes with telomere signal-free ends (SFEs), we examined these cell types for evidence of sister chromatid exchange at telomeres, and observed an increase in T-SCEs only in a subset of mTert-/- splenocytes or ES cells that possessed multiple SFEs. Furthermore, T-SCEs were more often detected in ES cells than in splenocytes that harbored a similar frequency of SFEs. In mTert heterozygous (mTert+/-) ES cells or splenocytes, which are known to exhibit a decrease in average telomere length but no SFEs, no increase in T-SCE was observed. In addition to T-SCE, other genomic rearrangements (i.e., SCE) were also significantly increased in mTert-/- ES cells possessing critically short telomeres, but not in splenocytes. Our results suggest that animals and cell culture differ in their ability to carry out genomic rearrangements as a means of maintaining telomere integrity when telomeres become critically shortened. |
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Authors:
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Yisong Wang; Natalie Erdmann; Richard J Giannone; Jun Wu; Marla Gomez; Yie Liu |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Date: 2005-07-06 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 102 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-07-20 Completed Date: 2005-10-26 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 10256-60 Citation Subset: IM |
Affiliation:
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Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6445, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals DNA-Binding Proteins / deficiency* Embryo, Mammalian / cytology* In Situ Hybridization, Fluorescence Mice Mice, Mutant Strains Sister Chromatid Exchange / genetics, physiology* Spleen / cytology Stem Cells / cytology* Telomerase / deficiency* Telomere / genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AG16629-03/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; EC 2.7.7.49/Telomerase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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