Caenorhabditis Elegans NHR-14/HNF4α Cooperates with cep-1/ p53 to Regulate DNA Damage-induced Apoptosis

Abstract Background: Nuclear hormone receptor is involved in transcriptional regulation and many important cellular processes including development and metabolism. However, its role in DNA damage-induced apoptosis remains elusive.Methods: Synchronized young adult animals were irradiated with different doses of gamma-Ray, and then put back to culture at 20 0 C. Germline cell apoptosis was scored at different time point.Results: Deletion of nhr-14 led to decreased DNA damage-induced germline apoptosis, but not the physiological programmed cell death. We also demonstrate that nhr-14 is not a checkpoint gene and functions downstream of the checkpoint pathway. Moreover, we show that nhr-14 regulates egl-1 and ced-13 transcription upon DNA damage. Mechanistically, NHR-14 and its human homolog hepatocyte nuclear factor 4 transcription factor alpha (HNF4α) form a complex with CEP-1/p53.Conclusions: Our results indicate that NHR-14/ HNF4α, in addition to its role as a nuclear hormone receptor, also cooperates with CEP-1/p53 to regulate DNA damage-induced apoptosis.