Role of p53 isoforms in the DNA damage response during Drosophila oogenesis

Ji-Hong Park1, Tram Thi Ngoc Nguyen1, Eun-Mi Lee2

  • 1Department of Biomedical Gerontology, Hallym University, Chuncheon, Gangwon-do, Republic of Korea.

Scientific Reports
|August 9, 2019
PubMed

Insights

The tumor suppressor p53, crucial for DNA damage response, has two isoforms in Drosophila. p53A is vital for maintaining germline stem cell function and fertility after irradiation.

Area of Science:

  • Developmental Biology
  • Genetics
  • Cell Biology

Background:

  • The tumor suppressor p53 plays a key role in DNA damage response, inducing cell cycle arrest or apoptosis.
  • Drosophila p53 has two isoforms, p53A and p53B, known to induce apoptosis in somatic cells.

Purpose of the Study:

  • To investigate the roles of Drosophila p53 isoforms in female germline cells' DNA damage response.
  • To determine the impact of p53 isoforms on germline stem cell function and fertility.

Main Methods:

  • Analysis of DNA damage response in adult ovaries after irradiation.
  • Assessment of cell death, egg production, and germline stem cell loss in wild-type and p53 mutant females.
  • Restoration of fertility by expressing p53A or p53B in germline cells of p53 mutant females.

Main Results:

  • Early oogenesis showed rapid, p53-dependent cell death after irradiation, involving both p53 isoforms.
  • Delayed cell death in mid-oogenesis was p53-independent and occurred only after high-dose irradiation.
  • High-dose irradiation in p53 mutant females led to reduced egg production and germline stem cell loss.
  • Expression of p53A, but not p53B, restored fertility in irradiated p53 mutant females.

Conclusions:

  • Both Drosophila p53 isoforms mediate early oogenesis cell death following DNA damage.
  • p53A is critical for maintaining germline stem cell function and female fertility, especially after irradiation.
  • p53B does not restore fertility, suggesting isoform-specific roles in the female germline.

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