Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53

Lei Sang1, Rui Dong1, Rui Liu2

  • 1Center for Life Sciences, School of Life Sciences, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, China.

Abstract

Insights

Nuclear hormone receptor NHR-14 is crucial for DNA damage-induced apoptosis by partnering with CEP-1/p53 to regulate gene transcription. This finding clarifies the role of nuclear hormone receptors in cellular stress responses.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • Nuclear hormone receptors regulate key cellular processes like development and metabolism.
  • The specific role of nuclear hormone receptors in DNA damage-induced apoptosis was previously unclear.

Purpose of the Study:

  • To investigate the role of nuclear hormone receptors in DNA damage-induced apoptosis.
  • To elucidate the molecular mechanisms underlying this process.

Main Methods:

  • Irradiation of young adult animals with varying doses of gamma-ray.
  • Culturing irradiated animals at 20°C and scoring germline cell apoptosis at different time points.

Main Results:

  • Deletion of nhr-14 significantly reduced DNA damage-induced germline apoptosis, but not physiological programmed cell death.
  • NHR-14 functions downstream of the DNA damage checkpoint pathway.
  • NHR-14 directly binds to the egl-1 promoter, forming a complex with CEP-1/p53 to promote egl-1 transcription.

Conclusions:

  • NHR-14 cooperates with CEP-1/p53 to regulate DNA damage-induced apoptosis.
  • This study identifies a novel role for NHR-14 in the cellular response to DNA damage.

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