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

Jeffery B Kerr; Karla J Hutt; Ewa M Michalak; Michele Cook; Cassandra Vandenberg; Seng H Liew; Philippe Bouillet; Alea A Mills; Clare L Scott; Jock K Findlay; Andreas Strasser

doi:10.1016/j.molcel.2012.08.017

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

Jeffery B Kerr, Karla J Hutt, Ewa M Michalak, Michele Cook, Cassandra Vandenberg, Seng H Liew, Philippe Bouillet, Alea A Mills, Clare L Scott, Jock K Findlay, Andreas Strasser

Anatomy & Developmental Biology

Research output: Contribution to journal › Article › Research › peer-review

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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 gamma-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 gamma-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.

Original language	English
Pages (from-to)	343 - 352
Number of pages	10
Journal	Molecular Cell
Volume	48
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2012.08.017
Publication status	Published - 2012

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Kerr, J. B., Hutt, K. J., Michalak, E. M., Cook, M., Vandenberg, C., Liew, S. H., Bouillet, P., Mills, A. A., Scott, C. L., Findlay, J. K., & Strasser, A. (2012). DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa. Molecular Cell, 48(3), 343 - 352. https://doi.org/10.1016/j.molcel.2012.08.017

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title = "DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa",

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 gamma-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 gamma-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.",

author = "Kerr, {Jeffery B} and Hutt, {Karla J} and Michalak, {Ewa M} and Michele Cook and Cassandra Vandenberg and Liew, {Seng H} and Philippe Bouillet and Mills, {Alea A} and Scott, {Clare L} and Findlay, {Jock K} and Andreas Strasser",

year = "2012",

doi = "10.1016/j.molcel.2012.08.017",

language = "English",

volume = "48",

pages = "343 -- 352",

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T1 - DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa

AU - Kerr, Jeffery B

AU - Hutt, Karla J

AU - Michalak, Ewa M

AU - Cook, Michele

AU - Vandenberg, Cassandra

AU - Liew, Seng H

AU - Bouillet, Philippe

AU - Mills, Alea A

AU - Scott, Clare L

AU - Findlay, Jock K

AU - Strasser, Andreas

PY - 2012

Y1 - 2012

N2 - 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 gamma-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 gamma-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.

AB - 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 gamma-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 gamma-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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496022/pdf/nihms400949.pdf

U2 - 10.1016/j.molcel.2012.08.017

DO - 10.1016/j.molcel.2012.08.017

M3 - Article

VL - 48

SP - 343

EP - 352

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 3

ER -

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

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