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Impeding DNA Break Repair Enables Oocyte Quality Control

Huanyu Qiao, H.B.D. Prasada Rao, Yan Yun, Sumit Sandhu, Jared H. Fong, Manali Sapre, Michael Nguyen, Addy Tham, Benjamin W. Van, Tiffany Y.H. Chng, Amy Lee, View ORCID ProfileNeil Hunter
doi: https://doi.org/10.1101/277913
Huanyu Qiao
University of California, Davis
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H.B.D. Prasada Rao
University of California, Davis
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Yan Yun
University of California, Davis
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Sumit Sandhu
University of California, Davis
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Jared H. Fong
University of California, Davis
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Manali Sapre
University of California, Davis
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Michael Nguyen
University of California, Davis
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Addy Tham
University of California, Davis
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Benjamin W. Van
University of California, Davis
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Tiffany Y.H. Chng
University of California, Davis
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Amy Lee
University of California, Davis
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Neil Hunter
University of California, Davis
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  • ORCID record for Neil Hunter
  • For correspondence: nhunter@ucdavis.edu
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Abstract

Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death is triggered by defects in chromosome synapsis and recombination, which involve repair of programmed DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocytes elimination in meiotic mutants require RNF212. RNF212 sensitizes cells to DSB-induced apoptosis within a narrow window when chromosomes desynapse during the transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a "memory" of meiotic defects that enables quality control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 07, 2018.
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Impeding DNA Break Repair Enables Oocyte Quality Control
Huanyu Qiao, H.B.D. Prasada Rao, Yan Yun, Sumit Sandhu, Jared H. Fong, Manali Sapre, Michael Nguyen, Addy Tham, Benjamin W. Van, Tiffany Y.H. Chng, Amy Lee, Neil Hunter
bioRxiv 277913; doi: https://doi.org/10.1101/277913
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Impeding DNA Break Repair Enables Oocyte Quality Control
Huanyu Qiao, H.B.D. Prasada Rao, Yan Yun, Sumit Sandhu, Jared H. Fong, Manali Sapre, Michael Nguyen, Addy Tham, Benjamin W. Van, Tiffany Y.H. Chng, Amy Lee, Neil Hunter
bioRxiv 277913; doi: https://doi.org/10.1101/277913

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