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<p>Female germ cells must preserve the integrity of their genome and generate genetic diversity via meiotic recombination. This challenging process is error prone. Highly conserved checkpoint pathways detect errors in recombination and DNA damage, inducing the death of defective oocytes. Nuclear Envelope Membrane Protein (NEMP) homologs are highly conserved proteins critical for fertility in flies, worms, fish and mice. They localize to the inner nuclear envelope where they provide mechanical support. However, why NEMP homologs are specifically required for fertility is still unclear. Using both <i>Drosophila</i> and mouse models, we establish that loss of NEMP homologs leads to activation of ATM and CHK2 kinases and inhibition of CHK2 or ATM rescues oocyte loss. In the absence of <i>Nemp1</i>, meiotic progression is delayed and DNA damage is increased at zygonema and pachynema stages. Loss of <i>Nemp1</i> also leads to defects in chromosome synapsis persisting through pachynema. We conclude that NEMP1 is needed to protect genome integrity and is crucial for accurate chromosome pairing and synapsis, supporting oocyte developmental competence and survival.</p>

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Loss of Nemp1 disrupts female meiosis and activates a conserved ATM-CHK2 checkpoint

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月24日

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  • Bilal Ahmad Hakim,
  • Yonit Tsatskis,
  • Ling Zhang,
  • Esther Choi,
  • Ying Zhang,
  • Didier Hodzic,
  • Que Wu,
  • MuYun Zhang,
  • Maryam Pashaei,
  • Kyungwon Ha,
  • Jannette Rusch,
  • Julie A. Brill,
  • Miguel Angel Brieño-Enríquez,
  • Andrea Jurisicova,
  • Helen McNeill

摘要

Female germ cells must preserve the integrity of their genome and generate genetic diversity via meiotic recombination. This challenging process is error prone. Highly conserved checkpoint pathways detect errors in recombination and DNA damage, inducing the death of defective oocytes. Nuclear Envelope Membrane Protein (NEMP) homologs are highly conserved proteins critical for fertility in flies, worms, fish and mice. They localize to the inner nuclear envelope where they provide mechanical support. However, why NEMP homologs are specifically required for fertility is still unclear. Using both Drosophila and mouse models, we establish that loss of NEMP homologs leads to activation of ATM and CHK2 kinases and inhibition of CHK2 or ATM rescues oocyte loss. In the absence of Nemp1, meiotic progression is delayed and DNA damage is increased at zygonema and pachynema stages. Loss of Nemp1 also leads to defects in chromosome synapsis persisting through pachynema. We conclude that NEMP1 is needed to protect genome integrity and is crucial for accurate chromosome pairing and synapsis, supporting oocyte developmental competence and survival.