Daniel Coutandin, Christian Osterburg, Ratnesh Kumar Srivastav, Manuela Sumyk, Sebastian Kehrlößer, Jakob Gebel, Marcel Tuppi, Jens Hannewald, Birgit Schäfer, Eidarus Salah, Sebastian Mathea, Uta Müller-Kuller, James Doutch, Manuel Grez, Stefan Knapp, Volker Dötsch
- Mammalian oocytes are arrested in the dictyate stage of meiotic prophase I for long periods of time, during which the high concentration of the p53 family member TAp63α sensitizes them to DNA damage-induced apoptosis. TAp63α is kept in an inactive and exclusively dimeric state but undergoes rapid phosphorylation-induced tetramerization and concomitant activation upon detection of DNA damage. Here we show that the TAp63α dimer is a kinetically trapped state. Activation follows a spring-loaded mechanism not requiring further translation of other cellular factors in oocytes and is associated with unfolding of the inhibitory structure that blocks the tetramerization interface. Using a combination of biophysical methods as well as cell and ovary culture experiments we explain how TAp63α is kept inactive in the absence of DNA damage but causes rapid oocyte elimination in response to a few DNA double strand breaks thereby acting as the key quality control factor in maternal reproduction.
MetadatenAuthor: | Daniel Coutandin, Christian OsterburgORCiDGND, Ratnesh Kumar Srivastav, Manuela Sumyk, Sebastian KehrlößerORCiDGND, Jakob Gebel, Marcel TuppiORCiDGND, Jens Hannewald, Birgit Schäfer, Eidarus Salah, Sebastian MatheaORCiD, Uta Müller-KullerGND, James Doutch, Manuel GrezGND, Stefan KnappORCiDGND, Volker DötschORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-444937 |
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DOI: | https://doi.org/10.7554/eLife.13909 |
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ISSN: | 2050-084X |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27021569 |
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Parent Title (English): | eLife |
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Publisher: | eLife Sciences Publications |
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Place of publication: | Cambridge |
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Contributor(s): | Joaquín M. Espinosa |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2017/10/26 |
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Year of first Publication: | 2016 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2017/10/26 |
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Tag: | DNA damage; E. coli; biophysics; cell biology; kinetically trapped state; mouse; oocytes; p63; quality control; spring-loaded activation; structural biolog |
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Volume: | 5 |
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Issue: | e13909 |
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Page Number: | 22 |
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First Page: | 1 |
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Last Page: | 22 |
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Note: | Copyright Coutandin et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
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HeBIS-PPN: | 446316695 |
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Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
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| Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus |
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| Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe |
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| Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) |
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Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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