Nuclear Envelope Membrane Protein 1 plays crucial and conserved roles in female meiosis

Female germ cells must preserve the integrity of their genome and generate genetic diversity via meiotic recombination. This challenging process, which occurs during fetal life, 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 inner nuclear membrane proteins which are critical for fertility in flies, worms, fish and mice, and mechanically support the nuclear envelope. However, why NEMP homologs are required for fertility is still unclear. Using both Drosophila and mouse models, we establish here that loss of Nemp1 leads to activation of an ATM-CHK2 DNA damage pathway and results in massive loss of oocytes during fetal life. Chemical or genetic inactivation of the ATM-CHK2-p63 pathway reduces oocyte loss, demonstrating its importance upon loss of Nemp1. 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 for timely and precise execution of meiotic prophase and is crucial for accurate pairing and synapsis, oocyte developmental competence and survival.