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PMID:15485914
Citation |
Sugo, N, Niimi, N, Aratani, Y, Takiguchi-Hayashi, K and Koyama, H (2004) p53 Deficiency rescues neuronal apoptosis but not differentiation in DNA polymerase beta-deficient mice. Mol. Cell. Biol. 24:9470-7 |
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Abstract |
In mammalian cells, DNA polymerase beta (Polbeta) functions in base excision repair. We have previously shown that Polbeta-deficient mice exhibit extensive neuronal cell death (apoptosis) in the developing nervous system and that the mice die immediately after birth. Here, we studied potential roles in the phenotype for p53, which has been implicated in DNA damage sensing, cell cycle arrest, and apoptosis. We generated Polbeta(-/-) p53(-/-) double-mutant mice and found that p53 deficiency dramatically rescued neuronal apoptosis associated with Polbeta deficiency, indicating that p53 mediates the apoptotic process in the nervous system. Importantly, proliferation and early differentiation of neuronal progenitors in Polbeta(-/-) p53(-/-) mice appeared normal, but their brains obviously displayed cytoarchitectural abnormalities; moreover, the mice, like Polbeta(-/-) p53(+/+) mice, failed to survive after birth. Thus, we strongly suggest a crucial role for Polbeta in the differentiation of specific neuronal cell types. |
Links |
PubMed PMC522222 Online version:10.1128/MCB.24.21.9470-9477.2004 |
Keywords |
Animals; Apoptosis/genetics; Cell Differentiation; Cell Division; DNA Polymerase beta/deficiency; DNA Polymerase beta/genetics; DNA Polymerase beta/metabolism; Genotype; Mice; Mice, Knockout; Nervous System/cytology; Nervous System/embryology; Nervous System/metabolism; Neurons/cytology; Neurons/metabolism; Phosphoserine/metabolism; Tumor Suppressor Protein p53/deficiency; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism |
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Significance
Annotations
Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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See also
References
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