The differentiated and conserved roles of Swi5‐Sfr1 in homologous recombination

Abstract

Homologous recombination (HR) is the process whereby two DNA molecules that share high sequence similarity are able to recombine to generate hybrid DNA molecules. Throughout evolution, the ability of HR to identify highly similar DNA sequences has been adopted for numerous biological phenomena including DNA repair, meiosis, telomere maintenance, ribosomal DNA amplification and immunological diversity. Although Rad51 and Dmc1 are the key proteins that promote HR in mitotic and meiotic cells, respectively, accessory proteins that allow Rad51 and Dmc1 to effectively fulfil their functions have been identified in all examined model systems. In this Review, we discuss the roles of the highly conserved Swi5‐Sfr1 accessory complex in yeast, mice and humans, and explore similarities and differences between these species.

Homologous recombination and the repair of DNA double-strand breaks

“…In eukaryotes, the Sae3-Mei5 heterodimer is important for mitotic and/or meiotic recombination, depending on the organism (50). For example, S. cerevisiae Sae3-Mei5 is only required for HR during meiosis, whereas in vertebrates the homologous complex SWI5-MEI5 functions during HR in somatic cells (Table 1).…”

“…Swi5-Sfr1, the fission yeast homologs, display an elongated structure that binds in the groove of the extended Rad51 filament (51). It stabilizes Rad51 filaments on ssDNA and promotes Rad51-dependent DNA strand exchange reactions (50). Mouse SWI5-SFR1 was shown to enhance the RAD51 ATPase by promoting ADP-ATP exchange (52).…”

Swi5–Sfr1 stimulates Rad51 recombinase filament assembly by modulating Rad51 dissociation

“…Several proteins stimulate and regulate Rad51 filament assembly (19)(20)(21)(22)(23)(24)(25)(26). Swi5 and Sfr1 were identified by genetic studies in the fission yeast Schizosaccharomyces pombe (27,28). Mutations in fission yeast swi5 and sfr1 decrease recombination rates and increase sensitivity to ionizing radiation and DNA-damaging chemicals (27,28).…”

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

“…The Mre11 nuclease, as part of the MRN complex, is the first detector of DSBs and initiates DNA resection in coordination with the actions of other nucleases and helicases, creating ssDNA overhangs at DSB sites [74]. This ssDNA region serves as a loading platform for the Rad51 recombinase to initiate homologous paring of the ssDNA and intact dsDNA template, which is followed by DNA synthesis [75]. Interestingly, cohesion establishment at DSBs depends not only on the Scc2-Scc4 loader, but also on Mre11, implying that ssDNA regions can be a target for second DNA capture by cohesin from the intact sister chromatid (Figure 2(c)) [72,73].…”