Enhanced pro-apoptosis gene signature following the activation of TAp63α in oocytes upon γ irradiation

Abstract

Specialized surveillance mechanisms are essential to maintain the genetic integrity of germ cells, which are not only the source of all somatic cells but also of the germ cells of the next generation. DNA damage and chromosomal aberrations are, therefore, not only detrimental for the individual but affect the entire species. In oocytes, the surveillance of the structural integrity of the DNA is maintained by the p53 family member TAp63α. The TAp63α protein is highly expressed in a closed and inactive state and gets activated to the open conformation upon the detection of DNA damage, in particular DNA double-strand breaks. To understand the cellular response to DNA damage that leads to the TAp63α triggered oocyte death we have investigated the RNA transcriptome of oocytes following irradiation at different time points. The analysis shows enhanced expression of pro-apoptotic and typical p53 target genes such as CDKn1a or Mdm2, concomitant with the activation of TAp63α. While DNA repair genes are not upregulated, inflammation-related genes become transcribed when apoptosis is initiated by activation of STAT transcription factors. Furthermore, comparison with the transcriptional profile of the ΔNp63α isoform from other studies shows only a minimal overlap, suggesting distinct regulatory programs of different p63 isoforms. mehr

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Titel	Enhanced pro-apoptosis gene signature following the activation of TAp63α in oocytes upon γ irradiation
Medien	Cell Death & Disease
Heft	3
Band	13
ISSN	2041-4889
Verfasser	Niclas Fester, Elisabeth Zielonka, Jakob Goldmann, Ann-Sophie Frombach, Uta Müller-Kuller, Niklas Gutfreund, Kristina Riegel, Jos Smits, Enrico Schleiff, Krishnaraj Rajalingam, Huiqing Zhou, Prof. Dr. Stefan Simm, Volker Dötsch
Seiten	204
Veröffentlichungsdatum	3.2022
Zitation	Fester, Niclas; Zielonka, Elisabeth; Goldmann, Jakob; Frombach, Ann-Sophie; Müller-Kuller, Uta; Gutfreund, Niklas; Riegel, Kristina; Smits, Jos; Schleiff, Enrico; Rajalingam, Krishnaraj; Zhou, Huiqing; Simm, Stefan; Dötsch, Volker (2022): Enhanced pro-apoptosis gene signature following the activation of TAp63α in oocytes upon γ irradiation. Cell Death & Disease 13 (3), 204. DOI: 10.1038/s41419-022-04659-2