The Yin and Yang of the MMS21–SMC5/6 SUMO ligase complex in homologous recombination

Maintaining genomic stability is critical for the prevention of disease. Numerous DNA repair pathways help to maintain genomic stability by correcting potentially lethal or disease-causing lesions to our genomes. Mounting evidence suggests that the post-translational modification sumoylation plays an important regulatory role in several aspects of DNA repair. The E3 SUMO ligase MMS21/NSE2 has gained increasing attention for its function in homologous recombination (HR), an error-free DNA repair pathway that mediates repair of double-strand breaks (DSBs) using the sister chromatid as a repair template. MMS21/NSE2 is part of the SMC5/6 complex, which has been shown to facilitate DSB repair, collapsed replication fork restart, and telomere elongation by HR. Here, I review the function of the SMC5/6 complex and its associated MMS21/NSE2 SUMO ligase activity in homologous recombination.