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Genetic recombination in meiosis plays an important role in generating diversity of genetic information. In yeast an Escherichia coli RecA-like gene, DMC1, is expressed in meiotic prophase and its product co-localizes with Rad51 protein on zygotene chromosomes. We have cloned the mouse and human homologs of the yeast DMC1 gene. The predicted human and mouse DMC1 proteins showed 54.1% sequence identity with yeast Dmc1 protein. The domain II region, highly conserved in the E.coli RecA-like protein family, was also found in the mammalian DMC1 proteins, including the two ATP binding motifs and DNA binding sites with the region. In situ hybridization analysis revealed expression of the mouse Dmc1 gene in testicular germ cells in meiosis; RT-PCR showed expression in embryonal ovaries. These findings suggest that DMC1 plays an important role in meiotic homologous recombination. From both the man and mouse we have isolated an alternative spliced form of Dmc1 cDNA (Dmc1-d), which is deleted for a region between the two motifs involved in nucleotide binding. Since the alternatively spliced Dmc1-d transcript was detected in both male and female germ cells, the encoded protein DMC1-D may have a novel role in mammalian genetic recombination in meiosis.