HOTSPOTS OF HOMOLOGOUS RECOMBINATION IN MOUSE MEIOSIS

High frequency of genetic recombination is characteristic of meiosis in all the eukaryotes. Although some of the enzymes and proteins involved in meiotic recombination have been identified in lower eukaryotes such as Saccharomyces cerevisiae (1, 2), little is known about the molecular machinery of meiotic recombination in higher eukaryotes. Both trans-acting factors, which include recombination enzymes, and chromosomal structure defined operationally in terms of cis-acting factors, play a role in meiotic recombination. In fact, genetic distance deduced from the frequency of meiotic recombination is not always proportional to the physical distance between two marker loci (3, 4). The discrepancy is due to variations in the frequency of recombination along DNA sequences on the chromosome. Recent advances in molecular analysis of meiotic recombination in the yeast S. cerevisiae display elevated frequency of homologous recombination and gene conversion at specific sites termed hotspots. Such hotspots are generally located in a potential promoter region adjacent to the 5'-end of an open reading frame (5, 6). Similar non-random distribution of recombination is also observed during human and mouse meiosis. Recombinational breakpoints in the proximal region of the mouse major histocompatibility complex (MHC) are not random but are clustered at four restricted segments, or hotspots (7-9). In this review, we characterize the molecular structure of these hotspots identified in the mouse MHC and demonstrate genetic control of recombination, focussing on one of the hotspots located close to the Lmp-2 gene.