A structural phylogenetic tree of Rad52 and its annealase superfamily.

Rad52, a highly conserved eukaryotic protein, plays a crucial role in DNA repair, particularly in double-strand break repair. Recent findings reveal that its distinct structural features, including a characteristic -sheet and -hairpin motif, are shared with the lambda phage single-strand annealing protein, Red, and other prokaryotic single-strand annealing proteins (SSAPs), indicating a common superfamily. Our analysis of over 10,000 SSAPs across all domains of life supports this hypothesis, confirming the presence of the characteristic motif despite variations in size and composition.