کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1939284 | 1050758 | 2007 | 6 صفحه PDF | دانلود رایگان |

In mammalian cells, DNA polymerase β (Polβ) and poly(ADP-ribose) polymerase-1 (PARP-1) have been implicated in base excision repair (BER) and single-strand break repair. Polβ knockout mice exhibit extensive neuronal apoptosis during neurogenesis and die immediately after birth, while PARP-1 knockout mice are viable and display hypersensitivity to genotoxic agents and genomic instability. Although accumulating biochemical data show functional interactions between Polβ and PARP-1, such interactions in the whole animal have not yet been explored. To study this, we generate Polβ−/−PARP-1−/− double mutant mice. Here, we show that the double mutant mice exhibit a profound developmental delay and embryonic lethality at mid-gestation. Importantly, the degree of the neuronal apoptosis was dramatically reduced in PARP-1 heterozygous mice in a Polβ null background. The reduction was well correlated with decreased levels of p53 phosphorylation at serine-18, suggesting that the apoptosis depends on the p53-mediated apoptosis pathway that is positively regulated by PARP-1. These results indicate that functional interactions between Polβ and PARP-1 play important roles in embryonic development and neurogenesis.
Journal: Biochemical and Biophysical Research Communications - Volume 354, Issue 3, 16 March 2007, Pages 656–661