NEMP1 organizes the meiotic telomere LINC interface to control chromosome movement and telomere integrity

Abstract

Nuclear Envelope Membrane Protein 1 (NEMP1) is highly expressed in oocytes and required for fertility, yet its meiotic function remains poorly understood. Here, we identify NEMP1 as a critical organizer of meiotic telomere-nuclear envelope coupling and chromosome dynamics. Loss of NEMP1 causes telomere aggregation, loss of shelterin protection, telomere shortening, persistent DNA damage, aberrant non-homologous end joining, and chromosome end-to-end fusion, ultimately leading to aneuploidy in mouse oocyte. NEMP1 is required during early fetal meiotic prophase I for telomere-nuclear envelope attachment, bouquet formation, homolog pairing, and synapsis. Live cell imaging revealed robust rapid prophase movements in wild-type meiocytes, which were nearly abolished by NEMP1 loss and restored by NEMP1-GFP re-expression. Mechanistically, NEMP1 associates with telomeric DNA and the SUN1-KASH5 LINC machinery, and SUN1-GFP restores chromosome movement in Nemp1-deficient meiocytes. Together, these findings establish NEMP1 as a nuclear-envelope organizer linking telomere protection, chromosome dynamics, and genome integrity during mammalian oogenesis.