title: Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex.
abstract: Homologous recombination (HR) represents a major error-free pathway to eliminate pre-carcinogenic chromosomal lesions. The DNA strand invasion reaction in HR is mediated by a helical filament of the Rad51 recombinase assembled on single-stranded DNA that is derived from the nucleolytic processing of the primary lesion. Recent studies have found that the human and mouse Swi5 and Sfr1 proteins form a complex that influences Rad51-mediated HR in cells. Here, we provide biophysical evidence that the mouse Swi5-Sfr1 complex has a 1:1 stoichiometry. Importantly, the Swi5-Sfr1 complex, but neither Swi5 nor Sfr1 alone, physically interacts with Rad51 and stimulates Rad51-mediated homologous DNA pairing. This stimulatory effect stems from the stabilization of the Rad51-ssDNA presynaptic filament. Moreover, we provide evidence that the RSfp (rodent Sfr1 proline rich) motif in Sfr1 serves as a negative regulatory element. These results thus reveal an evolutionarily conserved function in the Swi5-Sfr1 complex and furnish valuable information as to the regulatory role of the RSfp motif that is specific to the mammalian Sfr1 orthologs.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, No. 1, Section 4, Roosevelt Road, Taipei, 10617, Taiwan.
authors.forename: Shang-Pu
authors.initials: SP
authors.lastname: Tsai
authors.forename: Guan-Chin
authors.initials: GC
authors.lastname: Su
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Lin
authors.forename: Chan-I
authors.initials: CI
authors.lastname: Chung
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xue
authors.forename: Myun Hwa
authors.initials: MH
authors.lastname: Dunlop
authors.forename: Yufuko
authors.initials: Y
authors.lastname: Akamatsu
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
authors.forename: Peter
authors.initials: P
authors.lastname: Chi
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019281:Dimerization; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D051135:Rad51 Recombinase / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; C556302:Sfr1 protein, mouse; C556301:Swi5 protein, mouse; D051135:Rad51 Recombinase