Defying DNA double-strand break-induced death during prophase I meiosis by temporal TAp63? phosphorylation regulation in developing mouse oocytes.

ABSTRACT: The dichotomy in DNA damage sensitivity of developing mouse oocytes during female germ line development is striking. Embryonic oocytes withstand hundreds of programmed DNA double-strand breaks (DSBs) required for meiotic recombination. Postnatal immature oocytes fail to tolerate even a few DSBs induced by gamma radiation treatment. TAp63?, a p53 family member, undergoes phosphorylation and mediates postnatal immature oocyte death following gamma radiation treatment, which is thought important for germ line quality maintenance. Whether prenatal meiotic oocytes tolerate DNA DSBs simply because they lack TAp63? expression is not clear. We found a significant number of oocytes in newborn mice initiate TAp63? expression and simultaneously carry meiotic DNA DSBs. However, the risk of premature death appears unlikely, because newborn oocytes strongly abate TAp63? phosphorylation induction and resist normally lethal doses of ionizing radiation damage. A calyculin A-sensitive Ser/Thr phosphatase activity downregulates TAp63? phosphorylation and ATM kinase mediates phosphorylation. Possible alterations in the relative balance of these counteracting activities during development may first temper TAp63? phosphorylation and death induction during meiotic DNA DSB repair and recombination, and afterward, implement germ line quality control in later stages. Insights into inherent DNA DSB resistance mechanisms in newborn oocytes may help prevent infertility in women in need of radiation or chemotherapy.

SUBMITTER: Kim DA 

PROVIDER: S-EPMC3993582 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature