A Super New Twist on the Initiation of Meiotic Recombination

In Saccharomyces cerevisiae, it has been recognized for some time that the predominant stimulus of recombi-Rosenstiel Center and Department of Biology nation, both in mitosis and in meiosis, is the formation of double-strand breaks (DSBs). In mitotic cells, recom-Brandeis University Waltham, Massachusetts 02254 bination initiated by site-specific endonucleases such as HO (which initiates mating-type gene switching) or I-SceI (responsible for intron homing) have received great attention, and much is known about the sequence of molecular steps that occur after the creation of a DSB In meiosis, recombination between homologous chromosomes occurs at least 1000 times more frequently (Haber, 1995). The ends of a DSB are first resected by one or more 5Ј-to-3Ј exonucleases, producing long 3Ј-than it does in mitotic cells. This high level of genetic exchange does not simply provide a facile way to gener-ended single-stranded DNA that can invade an intact homologous donor sequence and initiate new DNA syn-ate diversity in sperm or eggs (or spores) from parents harboring hundreds of heterozygosities. Crossing-over thesis, leading to the repair of the DSB. A key step in understanding meiotic recombination came with the also serves a key role in ensuring that paired, homolo-gous chromosomes will properly segregate at the first observation that hot spots of meiotic recombination were also sites of DSBs, which were resected to produce meiotic division (for general reviews of meiotic recombi-nation, see Roeder, 1995; Kleckner, 1996). Chromo-3Ј-ended tails (Sun et al., 1991). Physical analysis of meiotic recombination also produced clear evidence of somes that fail to experience at least one crossover show very elevated rates of nondisjunction, leading to another expected intermediate in DSB-mediated recom-bination, the branched DNA structure known as a double aneuploid offspring. It has also been known for some time that topoisomerase II is necessary to disentangle Holliday junction (Schwaca and Kleckner, 1995). But how do meiotic DSBs arise and what is their rela-intertwined recombined chromsomes after recombina-tion; but surprisingly, a novel topoisomerease II is also tion to the restriction endonuclease-like cleavages made by HO and I-SceI? A search for mutation that needed to initiate recombination (Bergerat et al., 1997; Keeney et al., 1997). would prevent such cleavages and thus yield only nonre-combined (and nondisjoined) chromosomes provided Meiotic recombination is not simply the heating-up of a gently simmering process found in mitotic cells. There an embarrassment of riches: there are at least ten genes that are needed to induce meiotic recombination. How-are many …