The DNA damage response is required for oocyte cyst breakdown and follicle formation in mice.

PLoS Genetics
Ana Martínez-MarchalIgnasi Roig

Abstract

Mammalian oogonia proliferate without completing cytokinesis, forming cysts. Within these, oocytes differentiate and initiate meiosis, promoting double-strand break (DSBs) formation, which are repaired by homologous recombination (HR) causing the pairing and synapsis of the homologs. Errors in these processes activate checkpoint mechanisms, leading to apoptosis. At the end of prophase I, in contrast with what is observed in spermatocytes, oocytes accumulate unrepaired DSBs. Simultaneously to the cyst breakdown, there is a massive oocyte death, which has been proposed to be necessary to enable the individualization of the oocytes to form follicles. Based upon all the above-mentioned information, we hypothesize that the apparently inefficient HR occurring in the oocytes may be a requirement to first eliminate most of the oocytes and enable cyst breakdown and follicle formation. To test this idea, we compared perinatal ovaries from control and mutant mice for the effector kinase of the DNA Damage Response (DDR), CHK2. We found that CHK2 is required to eliminate ~50% of the fetal oocyte population. Nevertheless, the number of oocytes and follicles found in Chk2-mutant ovaries three days after birth was equivalent to that of the con...Continue Reading

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Citations

May 1, 2021·Frontiers in Cell and Developmental Biology·Funda M Kar, Andreas Hochwagen
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Xiaoyi Wang, Melissa E Pepling

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Methods Mentioned

BETA
genotyping
dissection

Software Mentioned

GraphPad Prism
Adobe Photoshop CC
Image Composite Editor

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