Open Accessp53 Deficiency Rescues Neuronal Apoptosis but Not Differentiation in DNA Polymerase β-Deficient Mice
Author(s) -
Noriyuki Sugo,
Naoko Niimi,
Yasuaki Aratani,
Keiko Takiguchi-Hayashi,
Hideki Koyama
Publication year - 2004
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.24.21.9470-9477.2004
Subject(s) - biology , apoptosis , programmed cell death , microbiology and biotechnology , progenitor cell , dna damage , cell cycle , cellular differentiation , dna repair , phenotype , poly adp ribose polymerase , polymerase , cancer research , dna , genetics , stem cell , gene
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.