Sacher Meik, Pfander Boris, Hoege Carsten, Jentsch Stefan
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Nat Cell Biol. 2006 Nov;8(11):1284-90. doi: 10.1038/ncb1488. Epub 2006 Oct 1.
Homologous recombination is essential for genetic exchange, meiosis and error-free repair of double-strand breaks. Central to this process is Rad52, a conserved homo-oligomeric ring-shaped protein, which mediates the exchange of the early recombination factor RPA by Rad51 and promotes strand annealing. Here, we report that Rad52 of Saccharomyces cerevisiae is modified by the ubiquitin-like protein SUMO, primarily at two sites that flank the conserved Rad52 domain. Sumoylation is induced on DNA damage and triggered by Mre11-Rad50-Xrs2 (MRX) complex-governed double-strand breaks (DSBs). Although sumoylation-defective Rad52 is largely recombination proficient, mutant analysis revealed that the SUMO modification sustains Rad52 activity and concomitantly shelters the protein from accelerated proteasomal degradation. Furthermore, our data indicate that sumoylation becomes particularly relevant for those Rad52 molecules that are engaged in recombination.
同源重组对于基因交换、减数分裂以及双链断裂的无差错修复至关重要。这一过程的核心是Rad52，它是一种保守的同型寡聚环状蛋白，介导早期重组因子RPA被Rad51取代，并促进链退火。在此，我们报道酿酒酵母的Rad52被类泛素蛋白SUMO修饰，主要在保守的Rad52结构域两侧的两个位点。SUMO化在DNA损伤时被诱导，并由Mre11-Rad50-Xrs2（MRX）复合物介导的双链断裂（DSB）触发。尽管SUMO化缺陷的Rad52在很大程度上仍具有重组能力，但突变分析表明，SUMO修饰维持了Rad52的活性，并同时保护该蛋白免受蛋白酶体加速降解。此外，我们的数据表明，SUMO化对于那些参与重组的Rad52分子尤为重要。
