Structural highlights
Function
RAD52_HUMAN Involved in double-stranded break repair. Plays a central role in genetic recombination and DNA repair by promoting the annealing of complementary single-stranded DNA and by stimulation of the RAD51 recombinase.[1]
Publication Abstract from PubMed
RAD52 mediates homologous recombination by annealing cDNA strands. However, the detailed mechanism of DNA annealing promoted by RAD52 has remained elusive. Here we report two crystal structures of human RAD52 single-stranded DNA (ssDNA) complexes that probably represent key reaction intermediates of RAD52-mediated DNA annealing. The first structure revealed a "wrapped" conformation of ssDNA around the homo-oligomeric RAD52 ring, in which the edges of the bases involved in base pairing are exposed to the solvent. The ssDNA conformation is close to B-form and appears capable of engaging in Watson-Crick base pairing with the cDNA strand. The second structure revealed a "trapped" conformation of ssDNA between two RAD52 rings. This conformation is stabilized by a different RAD52 DNA binding site, which promotes the accumulation of multiple RAD52 rings on ssDNA and the aggregation of ssDNA. These structures provide a structural framework for understanding the mechanism of RAD52-mediated DNA annealing.
Structural Basis of Homology-Directed DNA Repair Mediated by RAD52.,Saotome M, Saito K, Yasuda T, Ohtomo H, Sugiyama S, Nishimura Y, Kurumizaka H, Kagawa W iScience. 2018 May 25;3:50-62. doi: 10.1016/j.isci.2018.04.005. Epub 2018 Apr 12. PMID:30428330[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kitao H, Yuan ZM. Regulation of ionizing radiation-induced Rad52 nuclear foci formation by c-Abl-mediated phosphorylation. J Biol Chem. 2002 Dec 13;277(50):48944-8. Epub 2002 Oct 11. PMID:12379650 doi:10.1074/jbc.M208151200
- ↑ Saotome M, Saito K, Yasuda T, Ohtomo H, Sugiyama S, Nishimura Y, Kurumizaka H, Kagawa W. Structural Basis of Homology-Directed DNA Repair Mediated by RAD52. iScience. 2018 May 25;3:50-62. doi: 10.1016/j.isci.2018.04.005. Epub 2018 Apr 12. PMID:30428330 doi:http://dx.doi.org/10.1016/j.isci.2018.04.005
