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Human MMS21/NSE2 Is a SUMO Ligase Required for DNA Repair

机译：人类MMS21 / NSE2是DNA修复所需的SUMO连接酶

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DNA repair is required for the genomic stability and well-being of an organism. In yeasts, a multisubunit complex consisting of SMC5, SMC6, MMS21/NSE2, and other non-SMC proteins is required for DNA repair through homologous recombination. The yeast MMS21 protein is a SUMO ligase. Here we show that the human homolog of MMS21 is also a SUMO ligase. hMMS21 stimulates sumoylation of hSMC6 and the DNA repair protein TRAX. Depletion of hMMS21 by RNA interference (RNAi) sensitizes HeLa cells toward DNA damage-induced apoptosis. Ectopic expression of wild-type hMMS21, but not its ligase-inactive mutant, rescues this hypersensitivity of hMMS21-RNAi cells. ATM/ATR are hyperactivated in hMMS21-RNAi cells upon DNA damage. Consistently, hMMS21-RNAi cells show an increased number of phospho-CHK2 foci. Finally, we show that hMMS21-RNAi cells show a decreased capacity to repair DNA lesions as measured by the comet assay. Our findings suggest that the human SMC5/6 complex and the SUMO ligase activity of hMMS21 are required for the prevention of DNA damage-induced apoptosis by facilitating DNA repair in human cells.
机译：DNA修复对于生物体的基因组稳定性和健康是必需的。在酵母中，通过同源重组进行DNA修复需要由SMC5，SMC6，MMS21 / NSE2和其他非SMC蛋白组成的多亚基复合物。酵母MMS21蛋白是SUMO连接酶。在这里，我们显示MMS21的人类同源物也是SUMO连接酶。 hMMS21刺激hSMC6和DNA修复蛋白TRAX的磺酰化。 RNA干扰（RNAi）消耗hMMS21使HeLa细胞对DNA损伤诱导的细胞凋亡敏感。野生型hMMS21的异位表达可缓解hMMS21-RNAi细胞的这种超敏性，但异位表达不能激活连接酶。 DNA受损后，hMMS21-RNAi细胞中的ATM / ATR会被高度激活。一致地，hMMS21-RNAi细胞显示出磷酸-CHK2病灶数量增加。最后，我们显示hMMS21-RNAi细胞显示出修复彗星测定法测定的DNA损伤的能力降低。我们的发现表明，人SMC5 / 6复合物和hMMS21的SUMO连接酶活性是通过促进人细胞DNA修复来预防DNA损伤诱导的细胞凋亡所必需的。

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