p63 protects the female germ line during meiotic arrest.
Meiosis in the female germ line of mammals is distinguished by a prolonged arrest in prophase of meiosis I between homologous chromosome recombination and ovulation. How DNA damage is detected in these arrested oocytes is poorly understood, but it is variably thought to involve p53, a central tumour suppressor in mammals. While the function of p53 in monitoring the genome of somatic cells is clear, a consensus for the importance of p53 for germ line integrity has yet to emerge. Here we show that the p53 homologue p63 (refs 5, 6), and specifically the TAp63 isoform, is constitutively expressed in female germ cells during meiotic arrest and is essential in a process of DNA damage-induced oocyte death not involving p53. We also show that DNA damage induces both the phosphorylation of p63 and its binding to p53 cognate DNA sites and that these events are linked to oocyte death. Our data support a model whereby p63 is the primordial member of the p53 family and acts in a conserved process of monitoring the integrity of the female germ line, whereas the functions of p53 are restricted to vertebrate somatic cells for tumour suppression. These findings have implications for understanding female germ line fidelity, the regulation of fertility and the evolution of tumour suppressor mechanisms.
Suh
Eun-Kyung
EK
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Yang
Annie
A
Kettenbach
Arminja
A
Bamberger
Casimir
C
Michaelis
Ala H
AH
Zhu
Zhou
Z
Elvin
Julia A
JA
Bronson
Roderick T
RT
Crum
Christopher P
CP
McKeon
Frank
F
D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins