Nsmce2, also known as Mms21, is an essential SUMO ligase and a subunit of the SMC5/6 complex. The SMC5/6 complex is involved in maintaining chromatin structure, regulating gene expression, and protecting against genomic instability. Nsmce2-related SUMOylation participates in processes like DNA replication, repair, and chromosome segregation [2,3,4,5].

In mouse models, Nsmce2 deletion in adult mice leads to pathologies resembling those in Bloom's syndrome patients, with increased recombination rates and micronuclei accumulation, indicating its role in preventing cancer and aging [2]. In human Nsmce2-deficient cells, collapsed replication forks cannot be rescued effectively, resulting in increased mitotic DNA damage [3]. In zebrafish, knockdown of the Nsmce2 ortholog produces dwarfism [5]. In male germline stem cells of mice, Nsmce2 seems dispensable for proliferation, differentiation, and topological stress relief [7]. In breast cancer, high Nsmce2 expression is linked to poor prognosis and therapy resistance, and decreasing its expression can increase chemotherapy sensitivity [1]. In hepatocellular carcinoma, Nsmce2 promotes tumor development by regulating the SUMOylation of PPARα [6].

In summary, Nsmce2 is crucial for maintaining genomic integrity, playing significant roles in processes such as DNA damage response, cell cycle regulation, and preventing diseases like cancer, aging-related pathologies, and primordial dwarfism. Studies using gene knockout or knockdown models in mice, zebrafish, and cell lines have been instrumental in revealing these functions and their implications in disease, offering potential therapeutic targets for related diseases.