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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53 target gene AEN is a nuclear exonuclease required for p53-dependent apoptosis

T Kawase1, H Ichikawa, T Ohta

  • 1Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan.

Oncogene
|February 12, 2008
PubMed

Insights

Apoptosis-enhancing nuclease (AEN) is a novel p53 target gene that degrades DNA and RNA. AEN induces apoptosis and is crucial for DNA fragmentation in p53-dependent cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • DNA degradation is a hallmark of apoptosis, involving multiple nucleases.
  • Different stimuli may activate distinct nucleases, leading to varied DNA degradation patterns.

Purpose of the Study:

  • To identify and characterize a novel nuclease involved in p53-mediated apoptosis.
  • To elucidate the role of this nuclease in DNA fragmentation and cell death.

Main Methods:

  • Gene expression analysis to identify p53 target genes.
  • Biochemical assays to determine nuclease activity and substrate specificity (DNA and RNA).
  • Cellular localization studies and apoptosis assays.

Main Results:

  • Apoptosis-enhancing nuclease (AEN) is a direct p53 target gene, induced by DNA damage.
  • AEN is an exonuclease targeting single- and double-stranded DNA/RNA, essential for its apoptosis-inducing function.
  • AEN translocates from the nucleolus to the nucleoplasm during apoptosis, disrupting the nucleolus and facilitating DNA fragmentation.

Conclusions:

  • AEN is a novel, p53-regulated nuclease that plays a critical role in apoptosis.
  • AEN's nuclease activity and nucleolar translocation are essential for its function in DNA fragmentation and cell death induction.

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