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Maintaining genomic stability in the female germline

February 2011. Maintaining genomic stability in the female germline is extremely important for all species. Together with CEF colleagues and international collaborators, the research group of Volker Dötsch has revealed how the activity of quality control factor TAp63α is regulated in oocytes. Upon DNA damage, conformation of the protein changes from an inactive dimeric state to an active tetramer. Their results were published on 18 February in the journal Cell.

TAp63α, a homolog of the p53 tumor suppressor, is a quality control factor in the female germline. Undamaged oocytes already express high levels of the protein, which suggested that TAp63α's activity is under tight control of an inhibitory mechanism. The team showed that TAp63α is kept in an inactive dimeric state. Relief of inhibition leads to tetramer formation with ∼20-fold higher DNA affinity. In vivo, phosphorylation-triggered tetramerization of TAp63α is not reversible by dephosphorylation. The scientists could also show that a helix in the oligomerization domain of p63 is crucial for tetramer stabilization and competes with the transactivation domain for the same binding site. The findings demonstrate how TAp63α is inhibited by complex domain-domain interactions that provide the basis for regulating quality control in oocytes.


Prof. Volker Dötsch
Institut für Biophysikalische Chemie
Campus Riedberg
Tel.: (069) 798-29631
E-mail: vdoetsch@em.uni-frankfurt.de


G. B. Deutsch, E. M. Zielonka, D. Coutandin, T. A. Weber, B. Schäfer, J. Hannewald, L. M. Luh, F. G. Durst, M. Ibrahim, J. Hoffmann, F. H. Niesen, A. Sentürk, H. Kunkel, B. Brutschy, E. Schleiff, S. Knapp, A. Acker-Palmer, M. Grez, F. McKeon, V. Dötsch (2011). DNA Damage in Oocytes Induces a Switch of the Quality Control Factor TAp63α from Dimer to Tetramer. Cell, doi:10.1016/j.cell.2011.01.013. DOI 10.1016/j.cell.2011.01.013