The eukaryotic Rad51 protein is structurally and functionally related to the RecA gene product of Escherichia coli. Like RecA, RAD51 catalizes the strand transfer between homologous DNA molecules. This gene, in fact, is necessary for double strand break repair, and homologous recombination in mitosis and in meiosis. Other genes of S. cerevisiae, as RAD55, RAD57 and DMC1, are also homologous to RecA. DMC-1, in particular, performs functions very similar to RAD51, but is expressed specifically during meiosis. Dmc1 and Rad51 co-localize during meiotic prophase, and are likely to act together during meiotic recombination. Despite their similarities, these two proteins have specialized functions: Dmc1, unlike Rad51, does not interact with Rad52 and Rad54; Dmc1 complexes do not form in
rad51 mutants, while Rad51 complexes are retained in
dmc1 mutants. Genes homologous to RAD51 and DMC1 have been found in several eukaryotes (from fungi to mammals). In Drosophila melanogaster only the RAD51 homolog has been cloned so far. We have cloned and analysed the C. elegans RAD51 homologous locus and its regulation (see Rinaldo et al. Abstract, this same meeting). The CeRAD51 locus is transcribe as two alternative messenger RNAs potentially coding for proteins of different sizes: CeRad51L and CeRad51S. Although the C. elegans protein is more similar to the yeast Rad51 (62.3% of similarity, 47.7% of identity) than to the Dmc1 protein (57.8 of similarity, 46.4% of identity), we observe that in some positions, where CeRad51 diverges from the Rad51 eukaryotic consensus, the substitution coincides with the corresponding aminoacid in Dmc1 in at least one other species. If we look at the phylogenetic tree of the Rad51 sequence we note that the fungal sequences surprisingly seem to score much better than the CeRad51 sequence against the vertebrate Rad51. Although more than 80% of the C. elegans genome has already been sequenced and made available by the C. elegans Genome Sequence Consortium, we have been unable to the present moment to find any C. elegans gene or cDNA sequence corresponding to DMC1. This let us suppose that, in C. elegans, the DMC1 gene is not present. If this is the case, we can hypothesize that the gene duplication, at the origin of the evolution of RAD51 and DMC1 as independent genes, has been lost in the evolution of the nematode, and that in C. elegans a single gene is responsible for all the functions ascribed to the two loci in fungi as well as in vertebrates: the two different products coded by this single gene might be used at different stages and/or in different tissues. We propose a model of regulation at the transcriptional level: the two different transcripts can be activated by different transcription factors from two alternative promoters, one of which hidden within the first two exons and introns of this gene. In addition, the 38 extra aminoacids present at the aminoterminal end of CeRad51L might serves to bind other proteins conferring a different specificity or function to the protein.