SMC-5/6 complex subunit NSE-1 plays a crucial role in meiosis and DNA repair in Caenorhabditis elegans

Abstract

The SMC5/6 complex is evolutionarily conserved across all eukaryotes and plays a pivotal role in preserving genomic stability. Mutations in genes encoding SMC5/6 complex subunits have been associated with human lung disease, immunodeficiency, and chromosome breakage syndrome. Despite its critical importance, much about the SMC5/6 complex remains to be elucidated. Various evidences have suggested possible role of a subunit of the SMC5/6 complex, NSE1, in chromosome segregation and DNA repair. Current knowledge regarding the role of NSE1 is primarily derived from single-cell-based analyses in yeasts, Arabidopsis thaliana, and human cell lines. However, our understanding of its function is still limited and requires further investigation. This study delves into the role of nse-1 in Caenorhabditis elegans, revealing its involvement in meiotic recombination and DNA repair. nse-1 mutants display reduced fertility, increased male incidence, and increased sensitivity to genotoxic chemicals due to defects in meiotic chromosome segregation and DNA repair. These defects manifest as increased accumulation of RAD-51 foci, increased chromosome fragmentation, and susceptibility to MMS, cisplatin, and HU. Furthermore, nse-1 mutation exacerbates germ cell death by upregulating ced-13 and egl-1 genes involved in the CEP-1/p53-mediated apoptotic pathway. NSE-1 is essential for the proper localization of NSE-4 and MAGE-1 on the chromosomes. Collectively, these findings firmly establish nse-1 as a crucial factor in maintaining genomic stability.

Keywords: Apoptosis; C. elegans; DNA repair; Meiosis; Smc5/6 complex; nse-1.