The Rad52 protein plays important roles in the homologous recombinational repair (HRR) of double strand breaks of chromosomal DNA. In this study, we found that the human Rad52 protein catalyzed homologous pairing, which is an essential step for the HRR pathway. The N-terminal domain of Rad52 was identified as the homologous-pairing domain by a protease mapping experiment, and we determined the crystal structure of this homologous-pairing domain at 2.85 angstrom resolution, which revealed that the eleven monomers tightly associate into a ring. Surface potential analysis revealed that the positively charged groove encircles the Rad52 ring and contains well-conserved amino acid residues. Among the residues, those essential for ssDNA and dsDNA binding were actually identified by a mutational analysis. Thus, Rad52 is likely to bind DNA outside the undecameric ring. Furthermore, the structure of an ssDNA bound to Rad52 was determined by NMR spectroscopy, and was found to be extended about 1.5 times relative to the B-form DNA, which is similar to that bound to the bacterial homologous-pairing protein, RecA. [J Radiat Res 44:382 (2003)]