Human MMS21/NSE2 is a SUMO ligase required for DNA repair.

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.
Mesh Terms:
Amino Acid Sequence, Apoptosis, Cell Cycle Proteins, Cell Lineage, Comet Assay, DNA, DNA Damage, DNA Repair, DNA-Binding Proteins, Electrophoresis, Polyacrylamide Gel, Glutathione Transferase, Hela Cells, Humans, Immunoprecipitation, Ligases, Microscopy, Fluorescence, Models, Genetic, Molecular Sequence Data, Plasmids, Protein Biosynthesis, Protein Structure, Tertiary, RNA Interference, Recombination, Genetic, SUMO-1 Protein, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Schizosaccharomyces, Sequence Homology, Amino Acid, Time Factors, Ubiquitin-Conjugating Enzymes
Mol. Cell. Biol.
Date: Aug. 01, 2005
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