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The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

p53 deletion impairs clearance of chromosomal-instable stem cells in aging telomere-dysfunctional mice

Begus-Nahrmann, Yvonne, Lechel, André, Obenauf, Anna C, Nalapareddy, Kodandaramireddy, Peit, Elvira, Hoffmann, Eva, Schlaudraff, Falk, Liss, Birgit, Schirmacher, Peter, Kestler, Hans, Danenberg, Esther, Barker, Nick, Clevers, Hans, Speicher, Michael R, Rudolph, K Lenhard·2009·Nature Genetics
DOI 10.1038/ng.426
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Abstract

Telomere dysfunction limits the proliferative capacity of human cells and induces organismal aging by activation of p53 and p21. Although deletion of p21 elongates the lifespan of telomere-dysfunctional mice, a direct analysis of p53 in telomere-related aging has been hampered by early tumor formation in p53 knockout mice. Here we analyzed the functional consequences of conditional p53 deletion. Intestinal deletion of p53 shortened the lifespan of telomere-dysfunctional mice without inducing tumor formation. In contrast to p21 deletion, the deletion of p53 impaired the depletion of chromosomal-instable intestinal stem cells in aging telomere-dysfunctional mice. These instable stem cells contributed to epithelial regeneration leading to an accumulation of chromosomal instability, increased apoptosis, altered epithelial cell differentiation and premature intestinal failure. Together, these results provide the first experimental evidence for an organ system in which p53-dependent mechanisms prevent tissue destruction in response to telomere dysfunction by depleting genetically instable stem cells.

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Research works printed but not linked: 19

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Metadata

Authors
Begus-Nahrmann, Y., Lechel, A., Obenauf, A. C., Nalapareddy, K., Peit, E., Hoffmann, E., Schlaudraff, F., Liss, B., Schirmacher, P., Kestler, H., Danenberg, E., Barker, N., Clevers, H., Speicher, M. R., & Rudolph, K. L.
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2009-08-30
Volume
41
Issue
10
Pages
1138-1143
ISSN
  • 1061-4036
  • 1546-1718
DOI
10.1038/ng.426
Cited by
88
References
12
Language
en
Licence
www.springer.com/tdm (tdm)

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