Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex

Shang Pu Tsai, Guan Chin Su, Sheng Wei Lin, Chan I. Chung, Xiaoyu Xue, Myun Hwa Dunlop, Yufuko Akamatsu, Maria Jasin, Patrick Sung, Peter Chi

Research output: Contribution to journalArticle

22 Scopus citations

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 isspecific to themammalianSfr1 orthologs.

Original languageEnglish (US)
Pages (from-to)6558-6569
Number of pages12
JournalNucleic acids research
Volume40
Issue number14
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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