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Mol Cell. 2012 Nov 9;48(3):343-52. doi: 10.1016/j.molcel.2012.08.017. Epub 2012 Sep 20.

DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa.

Author information

1
Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3168, Australia.

Abstract

Trp63, a transcription factor related to the tumor suppressor p53, is activated by diverse stimuli and can initiate a range of cellular responses. TAp63 is the predominant Trp53 family member in primordial follicle oocyte nuclei and is essential for their apoptosis triggered by DNA damage in vivo. After γ-irradiation, induction of the proapoptotic BH3-only members Puma and Noxa was observed in primordial follicle oocytes from WT and Trp53(-/-) mice but not in those from TAp63-deficient mice. Primordial follicle oocytes from mice lacking Puma or both Puma and Noxa were protected from γ-irradiation-induced apoptosis and, remarkably, could produce healthy offspring. Hence, PUMA and NOXA are critical for DNA damage-induced, TAp63-mediated primordial follicle oocyte apoptosis. Thus, blockade of PUMA may protect fertility during cancer therapy and prevent premature menopause, improving women's health.

PMID:
23000175
PMCID:
PMC3496022
DOI:
10.1016/j.molcel.2012.08.017
[Indexed for MEDLINE]
Free PMC Article

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