# NSMCE2 dispensability in mouse spermatogenesis suggests functional redundancy within the meiotic repair network

## TL;DR

This study shows that NSMCE2 is not essential for mouse sperm production, suggesting other proteins can compensate for its absence.

## Contribution

The study reveals functional redundancy in the meiotic repair network, with PIAS1 potentially compensating for NSMCE2 deficiency.

## Key findings

- Germline deletion of Nsmce2 does not impair spermatogenesis or fertility in mice.
- PIAS1 is upregulated in Nsmce2-deficient testes, suggesting compensatory SUMOylation.
- Meiotic DNA repair and testicular architecture remain intact without NSMCE2.

## Abstract

NSMCE2, a SUMO E3 ligase subunit of the SMC5/6 complex, is essential for maintaining genomic integrity during mitosis, yet its meiotic function remains poorly understood. Here, we investigated the physiological role of NSMCE2 in male germ cells using a conditional knockout mouse model. Despite its high and stage-specific expression in testes, germline deletion of Nsmce2 resulted in no apparent impairment of spermatogenesis or fertility. Comprehensive analyses revealed normal testicular architecture, unaltered meiotic progression, intact DNA double-strand break repair, and stable transcriptomic profiles in Nsmce2-deficient testes. Mechanistically, we observed a specific upregulation of the SUMO E3 ligase PIAS1, which suggests a potential role in maintaining global SUMOylation homeostasis in the deficiency of NSMCE2. These findings demonstrate that NSMCE2 is dispensable for male fertility under physiological conditions. Such dispensability suggests that the meiotic DNA repair network possesses substantial functional redundancy and robust compensatory capacity, ensuring the maintenance of spermatogenic integrity even in the absence of a key repair factor. Collectively, our study highlights the resilient and fail-safe design of the mammalian meiotic system, which safeguards fertility through intrinsic robustness and molecular redundancy.

Infographic illustrates that NSMCE2 deficiency in germ cells does not disrupt key processes such as meiosis, spermiogenesis, testicular morphology, cell proliferation and apoptosis, fertility, or gross transcription, as all are marked with checkmarks, highlighting the redundancy that maintains spermatogenesis despite NSMCE2 loss.