Swi5, a protein-coding gene, forms the evolutionarily conserved Swi5-Sfr1 complex which plays a crucial role in homologous recombination, a process vital for maintaining genomic integrity [1,3]. This complex is involved in meiotic processes and DNA repair pathways, with its function being relevant to the proper functioning of cells in various organisms [1,2,3,4,5,7,8,9]. Genetic models, such as those in Schizosaccharomyces pombe, have been instrumental in studying Swi5's functions [1,2,4,5,6,7,9].

In fission yeast, phosphorylation of Swi5 and Sfr1 was observed during meiosis, though the functional significance of this phosphorylation remains unclear [1]. Mutations preventing phosphorylation of Swi5 and Sfr1 do not impair their function, while phosphomimetic mutants are only partially functional [1]. The Swi5-Sfr1 complex stimulates Dmc1-driven recombination in meiosis by enhancing Dmc1 filament assembly on single-stranded DNA, with Hop2-Mnd1 and Swi5-Sfr1 acting on different steps of this process [2]. In homologous recombination, Swi5-Sfr1 is an accessory complex that aids Rad51 and Dmc1 in fulfilling their functions in mitotic and meiotic cells respectively [3]. In fission yeast, Swi5 forms two distinct complexes, Swi5-Sfr1 and Swi5-Swi2, involved in homologous recombination and mating-type switching respectively [4]. The Swi5-Sfr1 complex has also been shown to be involved in Rad51-dependent recombinational repair, working independently of another mediator complex, Rhp55-Rhp57 [4]. Phosphorylation of Sfr1 in the Swi5-Sfr1 complex regulates its interaction with Rad51, and both over-and under-phosphorylation of Sfr1 lead to DNA repair defects [5]. The Swi5-Sfr1 complex stimulates the Rad51-promoted DNA strand exchange reaction by organizing DNA bases in the presynaptic filament, and it acts on Dmc1-and Rad51-driven DNA strand exchange through different mechanisms [6,7]. In mammalian cells, the SWI5-SFR1 complex in Mus musculus has a physical and functional interaction with RAD51, with the C-terminal domain of SWI5 contributing to this interaction, and this interaction is indispensable for stimulating RAD51's recombinase activity [8]. In Schizosaccharomyces pombe, two distinct sites within the N-terminus of Sfr1 cooperatively bind Rad51, and although deletion of this domain impairs Rad51 stimulation in vitro and renders cells sensitive to DNA damage, amino-acid substitution mutants can still promote DNA repair, with this repair being dependent on the Rad55-Rad57 complex, suggesting a collaborative role of Swi5-Sfr1 and Rad55-Rad57 in stimulating Rad51 [9].

In conclusion, Swi5, as part of the Swi5-Sfr1 complex, is essential for homologous recombination and DNA repair processes. Studies using yeast models have revealed its role in regulating key steps in these processes, such as filament assembly and strand exchange. Although no KO/CKO mouse models were mentioned in the provided references, the research on yeast models has significantly contributed to understanding the fundamental biological functions of Swi5, which may potentially provide insights into related disease mechanisms in higher organisms where similar pathways are likely conserved.

References:

1. Sevcovicova, Andrea, Plava, Jana, Gazdarica, Matej, Cipak, Lubos, Gregan, Juraj. 2021. Mapping and Analysis of Swi5 and Sfr1 Phosphorylation Sites. In Genes, 12, . doi:10.3390/genes12071014. https://pubmed.ncbi.nlm.nih.gov/34208949/

2. Lee, Wei, Iwasaki, Hiroshi, Tsubouchi, Hideo, Li, Hung-Wen. . Hop2-Mnd1 and Swi5-Sfr1 stimulate Dmc1 filament assembly using distinct mechanisms. In Nucleic acids research, 51, 8550-8562. doi:10.1093/nar/gkad561. https://pubmed.ncbi.nlm.nih.gov/37395447/

3. Argunhan, Bilge, Murayama, Yasuto, Iwasaki, Hiroshi. 2017. The differentiated and conserved roles of Swi5-Sfr1 in homologous recombination. In FEBS letters, 591, 2035-2047. doi:10.1002/1873-3468.12656. https://pubmed.ncbi.nlm.nih.gov/28423184/

4. Haruta, Nami, Akamatsu, Yufuko, Tsutsui, Yasuhiro, Arcangioli, Benoit, Iwasaki, Hiroshi. 2007. Fission yeast Swi5 protein, a novel DNA recombination mediator. In DNA repair, 7, 1-9. doi:. https://pubmed.ncbi.nlm.nih.gov/17716957/

5. Liang, Pengtao, Lister, Katie, Yates, Luke, Argunhan, Bilge, Zhang, Xiaodong. 2023. Phosphoregulation of DNA repair via the Rad51 auxiliary factor Swi5-Sfr1. In The Journal of biological chemistry, 299, 104929. doi:10.1016/j.jbc.2023.104929. https://pubmed.ncbi.nlm.nih.gov/37330173/

6. Fornander, Louise H, Renodon-Cornière, Axelle, Kuwabara, Naoyuki, Nordén, Bengt, Takahashi, Masayuki. 2013. Swi5-Sfr1 protein stimulates Rad51-mediated DNA strand exchange reaction through organization of DNA bases in the presynaptic filament. In Nucleic acids research, 42, 2358-65. doi:10.1093/nar/gkt1257. https://pubmed.ncbi.nlm.nih.gov/24304898/

7. Ito, Kentaro, Maki, Takahisa, Kanamaru, Shuji, Takahashi, Masayuki, Iwasaki, Hiroshi. . The Swi5-Sfr1 complex regulates Dmc1- and Rad51-driven DNA strand exchange proceeding through two distinct three-stranded intermediates by different mechanisms. In Nucleic acids research, 52, 12517-12533. doi:10.1093/nar/gkae841. https://pubmed.ncbi.nlm.nih.gov/39340300/

8. Su, Guan-Chin, Yeh, Hsin-Yi, Lin, Sheng-Wei, Lyu, Ping-Chiang, Chi, Peter. 2016. Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination. In Nucleic acids research, 44, 6242-51. doi:10.1093/nar/gkw375. https://pubmed.ncbi.nlm.nih.gov/27131790/

9. Argunhan, Bilge, Sakakura, Masayoshi, Afshar, Negar, Takahashi, Hideo, Iwasaki, Hiroshi. 2020. Cooperative interactions facilitate stimulation of Rad51 by the Swi5-Sfr1 auxiliary factor complex. In eLife, 9, . doi:10.7554/eLife.52566. https://pubmed.ncbi.nlm.nih.gov/32204793/