Preserving the integrity of the genome is crucial for the proper functioning and survival of the cell [1]. The structural maintenance of chromosomes (SMC) complexes, including cohesin, condensin and the Smc5/6 complex, play a major role in this process [1]. These complexes contribute to chromosome organization, chromosome segregation, gene expression, and DNA repair [2], [3]. Cohesin folds interphase chromosomes into topological domain loops and holds sister chromatids together, ensuring their equal segregation. Condensin, on the other hand, organizes the genome by compacting mitotic chromosomes into hierarchically nested loops. Although the specific roles of the Smc5/6 complex in genome maintenance are not as well understood as those of cohesin and condensin, continuous research is revealing new insights [1].

Recent studies highlighted the versatile role of the Smc5/6 complex in DNA loop extrusion, telomere maintenance, and even antiviral defense [1]. However, much remains to be uncovered about this complex. The cryogenic electron microscopy (cryo-EM) structure of DNA-bound Saccharomyces cerevisiae Smc5/6 complex revealed intricate interactions among Smc5, Smc6, and the Nse1-3-4 subcomplex encircling the DNA double helix [4]. Data from Tandem mass spectrometry (MS/MS) analysis suggest that domain arrangements and orientation of the human hNSE1-hNSE3-hNSE4 subcomplex is localized at the SMC head domains, with a partially or fully opened hSMC5-hSMC6 [5]. Our previous studies have demonstrated the trimeric interaction of NSE-1-3-4 in C. elegans, showing that the chromosome localization of NSE-1 depends on MAGE-1 [6] and NSE-4 [7]. Nse1 binding to the Nse4 linker increases the stability of the ATP-free SMC5/6 complex and facilitates the opening of the SMC5/6 complex upon ATP binding [8]. In humans, mutations in the hNSE1-hNSE3-hNSE4 subcomplex can lead to lung disease, immunodeficiency, and chromosome breakage syndrome [9]. In the budding yeast S. cerevisiae, mutations in the region of Nse1 that accepts the Smc5-loop result in slow growth and a global reduction in the chromatin-associated portion of the Smc5/6 complex [10].

Our current knowledge of Nse1 primarily stems from single-cell-based analyses in yeasts, A. thaliana, and human cell lines, and remains limited. Hence, exploring its function in different model organisms is essential to gain a broader and more comprehensive understanding. In this study, we characterized nse-1 in C. elegans, a suitable animal system for investigating DNA damage response. Our results highlight the crucial role of nse-1 in meiotic recombination and DNA repair. Furthermore, our study affirms the significance of NSE-1 in the chromosome localization of MAGE-1 and NSE-4.