Loss of NSE-4 Perturbs Genome Stability and DNA Repair in Caenorhabditis elegans

Abstract

The Structural Maintenance of Chromosomes (SMC) complex plays an important role in maintaining chromosome integrity, in which the SMC5/6 complex occupies a central position by facilitating mitotic and meiotic processes as well as DNA repair. NSE-4 Kleisin is critical for both the organization and function of the SMC5/6 complex, bridging NSE1 and NSE3 (MAGE related) with the head domains of the SMC5 and SMC6 proteins. Despite the conservation in protein sequence, no functional relevance of the NSE-4 homologous protein (NSE-4) in Caenorhabditis elegans has been reported. Here, we demonstrated the essential role of C. elegans NSE-4 in genome maintenance and DNA repair. Our results showed that NSE-4 is essential for the maintenance of chromosomal structure and repair of a range of chemically induced DNA damage. Furthermore, NSE-4 is involved in inter-sister repair during meiosis. NSE-4 localizes on the chromosome and is indispensable for the localization of NSE-1. Collectively, our data from this study provide further insight into the evolutionary conservation and diversification of NSE-4 function in the SMC-5/6 complex.

How Chromatin Motor Complexes Influence the Nuclear Architecture: A Review of Chromatin Organization, Cohesins, and Condensins with a Focus on C. elegans

“…The SMC-5/6 complex is made up of the final SMC proteins SMC-5 and SMC-6, a kleisin NSE-4, and up to five regulatory proteins (see Table 4) [70,71]. Generally, the SMC-5/6 complex functions in DNA replication, DNA repair, and silencing of extra-chromosomal DNA [72,73]. In C. elegans, it has been shown that the SMC-5/6 complex processes double-stranded breaks in meiosis and prevents ectopic recombination [74].…”