Abstract
Rad52, a highly conserved eukaryotic protein, plays a crucial role in DNA repair, especially in double-strand break repair. Recent findings reveal that its distinct structural features, including a characteristic β-sheet and β-hairpin motif, are shared with the lambda phage single-strand annealing proteins, Redβ, indicating a common superfamily. Our analysis of over 10,000 single-strand annealing proteins (SSAPs) across all kingdoms of life supports this hypothesis, confirming their possession of the characteristic motif despite variations in size and composition. We found that archaea, representing only 1\% of the studied proteins, exhibit most of these variations. Through the examination of four representative archaeal SSAPs, we elucidate the structural relationship between eukaryotic and bacterial SSAPs, highlighting differences in β-sheet size and β-hairpin complexity. Furthermore, we identify an archaeal SSAP with a structure nearly identical to the human variant and screen over 100 million unannotated proteins for potential SSAP candidates. Our computational analysis complements existing sequence with structural evidence supporting the suggested orthology among five SSAP families across all kingdoms: Rad52, Redβ, RecT, Erf, and Sak3.Competing Interest StatementThe authors have declared no competing interest.All data used to generate this work are accessible via the link provided below. This collection includes both raw and generated data. The raw data consists of PDB files for all SSAP proteins and their FASTA sequences. The generated data encompass BLAST results (sequence data), structural alignments (TM scores), taxonomy information, and family memberships from InterPro. Please refer to the following link to access the data.Raw data: ./rawData/PDBs, FastaAlignment results: ./alignments/https://sharing.biotec.tu-dresden.de/index.php/s/vNrJ3aHLSUN6kZE
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