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MMS21, also known as NSE2, is a SUMO ligase that in combination with the SMC5/6 complex is required for the prevention of DNA damage induced apoptosis by facilitating DNA repair in human cells. MMS21-dependent sumoylation is integral and important to the cohesion mechanism and mitotic progression; this function appears to be independent of SMC6. MMS21 mediates SUMO attachment to various proteins such as SMC6L1 and TRAX, and possibly the cohesin components RAD21 and STAG2.