title: Mechanistic insights into the activation of Rad51-mediated strand exchange from the structure of a recombination activator, the Swi5-Sfr1 complex.
abstract: Rad51 forms a helical filament on single-stranded DNA and promotes strand exchange between two homologous DNA molecules during homologous recombination. The Swi5-Sfr1 complex interacts directly with Rad51 and stimulates strand exchange. Here we describe structural and functional aspects of the complex. Swi5 and the C-terminal core domain of Sfr1 form an essential activator complex with a parallel coiled-coil heterodimer joined firmly together via two previously uncharacterized leucine-zipper motifs and a bundle. The resultant coiled coil is sharply kinked, generating an elongated crescent-shaped structure suitable for transient binding within the helical groove of the Rad51 filament. The N-terminal region of Sfr1, meanwhile, has an interface for binding of Rad51. Our data suggest that the snug fit resulting from the complementary geometry of the heterodimer activates the Rad51 filament and that the N-terminal domain of Sfr1 plays a role in the efficient recruitment of the Swi5-Sfr1 complex to the Rad51 filaments.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kuwabara
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Murayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Yuuichi
authors.initials: Y
authors.lastname: Kokabu
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ikeguchi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Sato
authors.forename: Kouta
authors.initials: K
authors.lastname: Mayanagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsutsui
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D018360:Crystallography, X-Ray; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D051135:Rad51 Recombinase / Q000737:chemistry*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry*
chemical_list: D046912:Multiprotein Complexes; C084232:RHP51 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C514357:Sfr1 protein, S pombe; C483769:Swi5 protein, S pombe; D051135:Rad51 Recombinase