TY  - JOUR
A1  - Fester, Niclas
A1  - Zielonka, Elisabeth
A1  - Goldmann, Jakob
A1  - Frombach, Ann-Sophie
A1  - Müller-Kuller, Uta
A1  - Gutfreund, Niklas
A1  - Riegel, Kristina
A1  - Smits, Jos G. A.
A1  - Schleiff, Enrico
A1  - Rajalingam, Krishnaraj
A1  - Zhou, Huiqing
A1  - Simm, Stefan
A1  - Dötsch, Volker
T1  - Enhanced pro-apoptosis gene signature following the activation of TAp63α in oocytes upon γ irradiation
T2  - Cell death & disease
N2  - 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.
KW  - Mechanisms of disease
KW  - Radiotherapy
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/69526
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-695262
SN  - 2041-4889
N1  - Open Access funding enabled and organized by project DEAL.
N1  - The research was funded by the DFG (DO 545/18-1), the collaborative research centers SFB902 and SFB1292, and the Centre for Biomolecular Magnetic Resonance (BMRZ).
VL  - 13
IS  - 204
SP  - 1
EP  - 10
PB  - London [u.a.]
CY  - Nature Publishing Group
ER  -