Control of Rad52 recombination activity by double-strand break-induced SUMO modification.
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.
Sacher
Meik
M
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Pfander
Boris
B
Hoege
Carsten
C
Jentsch
Stefan
S
D015153:Blotting, Western; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D004271:DNA, Fungal; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae