A common structural core in proteins active in DNA recombination and replication.

Although DNA recombination, replication, repair and transcription have historically been studied as separate processes, we now understand that many of these pathways are intimately related. A growing body of data suggest that the RecA superfamily of proteins is central to both the replication and recombination pathways. Structural studies have revealed that all of these proteins share a highly conserved nucleotide-binding core with the E. coli RecA protein. Representative structures (determined by X-ray crystallography or electron microscopy) of proteins from this superfamily illustrate how these DNA-binding proteins, which perform a variety of functions, might utilize the same highly conserved core.The E. coli RecA protein1xStorey, R.M. et al. Nature. 1992; 355: 318–325Crossref | PubMedSee all References1 has a nucleotide- and DNA-binding core, comprising a central β sheet and associated α helices. The protein polymerizes into helical filaments on DNA (providing a scaffold for homologous recombination) or forms hexameric rings2xYu, X. and Egelman, E.H. Nat. Struct. Biol. 1997; 4: 101–104Crossref | PubMed | Scopus (105)See all References2.The yeast Rad51 protein6xShinohara, A et al. Cell. 1992; 69: 457–470Abstract | Full Text PDF | PubMed | Scopus (860)See all References, 7xAboussekhra, A. et al. Mol. Cell Biol. 1992; 12: 3224–3234PubMedSee all References, a functional homolog of RecA, forms helical filaments on DNA that serve as a scaffold in which homologous recombination is initiated8xOgawa, T. et al. Science. 1993; 259: 1896–1899Crossref | PubMedSee all References8. A three dimensional reconstruction of a filament formed by human RAD51 bound to a single-stranded DNA is shown (X, Yu, S. West and E. Egelman, unpublished).The Dmc1 protein is a eukaryotic meiosis-specific recombinase11xBishop, D.K. et al. Cell. 1992; 69: 439–456Abstract | Full Text PDF | PubMed | Scopus (754)See all References11. Whereas RecA and Rad51 appear to function mainly as helical filaments, human DMC1 binds in vitro to DNA as an octameric ring only, with the DNA bound in the central channel12xPassy, S.I. et al. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 10684–10688Crossref | PubMed | Scopus (102)See all References12.The primary replicative helicase (i.e. a protein that promotes the ATP-dependent unwinding of double-stranded DNA) of bacteriophage T4 is the gp4 protein. The crystal structure of a large fragment of this helicase has been solved3xSawaya, M.R. et al. Cell. 1999; 99: 167–177Abstract | Full Text | Full Text PDF | PubMedSee all References3, and it is shown superimposed on an electron microscopic structure of the intact gp4b hexameric ring4xEgelman, F.H. et al. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 3869–3873Crossref | PubMedSee all References4. Single-stranded DNA passes through the central channel of this ring, providing a mechanism for strand separation, with the complementary strand displaced outside of the ring5xYu, X. et al. Nat. Struct. Biol. 1996; 3: 740–743Crossref | PubMed | Scopus (109)See all References5.The δ′ subunit of the E. coli clamp-loader complex is involved in loading the processivity factor around the DNA as part of the replication apparatus. The δ′ protein does not bind to ATP, but it has the same nucleotide-binding fold as the RecA protein13xGuenther, B. et al. Cell. 1997; 91: 335–345Abstract | Full Text | Full Text PDF | PubMed | Scopus (201)See all References13. This suggests that a strong structural conservation exists between these proteins, yet sequences and functions display no significant similarity.PcrA (Bacillus stearothermophilus) was the first helicase to be solved at atomic resolution9xSubramanya, H.S. et al. Nature. 1996; 384: 379–383Crossref | PubMed | Scopus (354)See all References9. Studies of complexes of PcrA with different DNA substrates suggested an ‘inchworm’ mechanism for how PcrA functions in strand separation10xVelankar, S.S. et al. Cell. 1999; 97: 75–84Abstract | Full Text | Full Text PDF | PubMedSee all References10. In this model, the monomeric protein slides along the DNA by undergoing large conformational changes from one DNA-binding site to the next, which creates an alternating bind—release-type mechanism. However, not all helicases function this way: for example, gp4 appears to function by only binding to single-stranded DNA.