TY  - JOUR
A1  - Coutandin, Daniel
A1  - Osterburg, Christian
A1  - Srivastav, Ratnesh Kumar
A1  - Sumyk, Manuela
A1  - Kehrlößer, Sebastian
A1  - Gebel, Jakob
A1  - Tuppi, Marcel
A1  - Hannewald, Jens
A1  - Schäfer, Birgit
A1  - Salah, Eidarus
A1  - Mathea, Sebastian
A1  - Müller-Kuller, Uta
A1  - Doutch, James
A1  - Grez, Manuel
A1  - Knapp, Stefan
A1  - Dötsch, Volker
T1  - Quality control in oocytes by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level
T2  - eLife
N2  - 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.
KW  - DNA damage
KW  - E. coli
KW  - biophysics
KW  - cell biology
KW  - kinetically trapped state
KW  - mouse
KW  - oocytes
KW  - p63
KW  - quality control
KW  - spring-loaded activation
KW  - structural biolog
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44493
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-444937
SN  - 2050-084X
N1  - 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.
VL  - 5
IS  - e13909
SP  - 1
EP  - 22
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -