ATR is a master regulator of the oocyte meiotic prophase checkpoint
- 1Zhejiang University
Abstract
During meiotic prophase, programmed double-strand breaks (DSBs) initiate meiotic recombination, and defects in this process result in persistent DSBs and chromosome asynapsis, triggering checkpoint-mediated oocyte elimination before primordial follicle formation. However, how the oocyte meiotic prophase checkpoint is regulated remains unclear. ATR is a DNA damage response kinase essential for male meiosis, but its role in female meiosis is poorly characterized. Here, we identify ATR as a master regulator of the oocyte meiotic prophase checkpoint. ATR loss fully rescues the survival of Dmc1-/- oocytes, which exhibit persistent DSBs and extensive chromosome asynapsis. ATR loss also fully rescues the survival of asynaptic Spo11-/- oocytes and Trip13-/- oocytes with aberrant checkpoint activation, demonstrating an essential role for ATR in the chromosome asynapsis checkpoint. Mechanistically, BRCA1 is required for ATR localization to unsynapsed chromosome axes, whereas ATR is dispensable for BRCA1 localization, establishing a BRCA1-ATR regulatory hierarchy at unsynapsed chromosome axes that is conserved between oocytes and spermatocytes. Together, these findings place ATR at the center of the oocyte meiotic prophase checkpoint and define a BRCA1-ATR signaling axis that links chromosome asynapsis to oocyte elimination.
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BibTeX
@misc{li2026master,
title = {{ATR is a master regulator of the oocyte meiotic prophase checkpoint}},
author = {J. Li and X. Jiao and L. Bai and Y. Wang and Y. Zhu and Y. Liu and L.-Y. Lu},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758727},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758727v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - ATR is a master regulator of the oocyte meiotic prophase checkpoint
AU - J. Li
AU - X. Jiao
AU - L. Bai
AU - Y. Wang
AU - Y. Zhu
AU - Y. Liu
AU - L.-Y. Lu
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758727
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758727v1
AB - During meiotic prophase, programmed double-strand breaks (DSBs) initiate meiotic recombination, and defects in this process result in persistent DSBs and chromosome asynapsis, triggering checkpoint-mediated oocyte elimination before primordial follicle formation. However, how the oocyte meiotic prophase checkpoint is regulated remains unclear. ATR is a DNA damage response kinase essential for male meiosis, but its role in female meiosis is poorly characterized. Here, we identify ATR as a master regulator of the oocyte meiotic prophase checkpoint. ATR loss fully rescues the survival of Dmc1-/- oocytes, which exhibit persistent DSBs and extensive chromosome asynapsis. ATR loss also fully rescues the survival of asynaptic Spo11-/- oocytes and Trip13-/- oocytes with aberrant checkpoint activation, demonstrating an essential role for ATR in the chromosome asynapsis checkpoint. Mechanistically, BRCA1 is required for ATR localization to unsynapsed chromosome axes, whereas ATR is dispensable for BRCA1 localization, establishing a BRCA1-ATR regulatory hierarchy at unsynapsed chromosome axes that is conserved between oocytes and spermatocytes. Together, these findings place ATR at the center of the oocyte meiotic prophase checkpoint and define a BRCA1-ATR signaling axis that links chromosome asynapsis to oocyte elimination.
ER -