Fig. 1: Possible fidelity-controlling residues of DMC1 and RAD51.

a Alignment of the amino acid residues in the Loop 1 and Loop 2 of DNA recombinases from H. sapiens (Hs), M. musculus (Mm), S. cerevisiae (Sc), and E. coli (Ec). All asterisks denote Loop 1 and Loop 2 lineage-specific amino acids, whereas red asterisks denote the three key residues identified in this study. Three conserved residues also addressed in this study are indicated by a + sign. b, c Inter-triplet area of DMC1 and RAD51 (PDB 5H1B²⁸) in the presynaptic filament. d, e The same as b, c, except for the postsynaptic filaments of DMC1 and RAD51 (PDB 5H1C²⁸). f Stereo view of the superposed d and e. The conserved residues DMC1 R236 and L239 from Loop 1, and the lineage-specific residues DMC1 P274 and G275 from Loop 2 are shown in sticks. The labels of DMC1 protomers are based on the designation of RAD51 protomers interacting with a nucleotide triplet from 5′ to 3′ as RAD51-5′, RAD51-0, and RAD51-3′ as described in Xu et al.²⁸. g A schematic model showing the three lineage-specific residues (bolded) coordinating with three conserved residues (non-bolded) to contribute to the mismatch tolerance (low fidelity) of DMC1 and the unstable mismatch (high fidelity) of RAD51.