Cohesins are required for meiotic DNA breakage and recombination in Schizosaccharomyces pombe

Abstract

In preparation for the unique segregation of homologs at the first meiotic division, chromosomes undergo dramatic changes. The meiosis-specific sister chromatid cohesins Rec8 and Rec11 of Schizosaccharomyces pombe are recruited around the time of premeiotic replication, and Rec10, a component of meiosis-specific linear elements, is subsequently added. Here we report that Rec10 is essential for meiosis-specific DNA breakage by Rec12 (Spo11 homolog) and for meiotic recombination. DNA breakage and recombination also depend on the Rec8 and Rec11 cohesins, strictly in some genomic intervals but less so in others. Thus, in addition to their previously recognized role in meiotic chromosome segregation, cohesins have a direct role, as do linear element components, in meiotic recombination by enabling double-strand DNA break formation by Rec12. Our results reveal a pathway, whose regulation is significantly different from that in the distantly related yeast Saccharomyces cerevisiae, for meiosis-specific chromosome differentiation and high-frequency recombination.linear elements ͉ meiotic recombination ͉ regional specificity T he cardinal feature of meiosis is the reduction of chromosome number from diploid to haploid. Although chromosomes are replicated only once in meiosis, there are two nuclear divisions. In the first division (meiosis I, or MI) homologs, rather than sister chromatids, segregate from each other, a process that requires mutual recognition of homologs. Specific recognition is provided by high-frequency meiotic recombination, normally between allelic positions on homologs rather than sister chromatids. Recombination provides physical connections between homologs, in the form of one or more crossovers, which allow tension to form when homologs are properly positioned to segregate to opposite poles of the cell at MI. At the second division (meiosis II) sister centromeres segregate from each other, as in a normal mitotic division.The unique behavior of chromosomes during meiosis requires certain meiosis-specific proteins, collectively called chromosomal core proteins, that modify sister chromatid cohesion, homolog juxtaposition and segregation, recombination, and perhaps replication. In the fission yeast Schizosaccharomyces pombe, the meiosis-specific cohesins Rec8 and Rec11 are recruited to chromosomes at or about the time of premeiotic replication (1, 2). Rec8 and Rec11 share sequence similarity with the S. pombe mitotic cohesins Rad21 and Psc3, respectively; rec8 and rec11 mutants manifest defects in meiotic sister chromatid cohesion and homolog segregation (1-3). Many organisms express a meiosis-specific Rec8 protein; like S. pombe, mice and humans express in addition a meiosis-specific Rec11-like protein, called STAG3, although the distantly related budding yeast Saccharomyces cerevisiae does not (4). Despite their important roles in chromosome segregation, the rec8 and rec11 genes were first identified by mutations that strongly reduce meiotic recombination at ade6 (5). These observations indicate a cl...

Linear Element-Independent Meiotic Recombination in Schizosaccharomyces pombe

“…These results indicate that Rec10 plays a role in regulating both crossing over and gene conversion throughout the genome and not only in restricted regions, as previously reported. This finding corroborates a similar finding made recently by Ellermeier and Smith (2005), who employed a rec10D mutant. Moreover, there is a differential requirement for a function of Rec10 for controlling gene conversions; this function is lost in the rec10-155 mutant (see discussion).…”

“…This includes loci at which we observed only relatively minor reductions. For example, the rec10-155 mutation results in a 2-fold reduction in intergenic recombination at the ura1-pro1 interval on chromosome I, while the rec10-175 null mutation gives a 42-fold reduction at this interval (Ellermeier and Smith 2005). We confirmed the differences between rec10-155 and rec10-175 by measuring pro1-ura1 intergenic recombination and ura1 intragenic recombination for both mutants under identical conditions (Table 2; data not shown).…”

“…The similar regional pattern of recombination in the rec10-109 and cohesion mutants indicate that there is an intimate functional association between meiotic cohesins and LinEs. However, recent studies demonstrate that Rec10 is required to regulate recombination more widely throughout the genome, indicating that the middle region regulation pattern exposed by the study of rec10-109 is allele specific (Ellermeier and Smith 2005; this study).…”

“…In addition, intragenic recombination at the ura1 locus was reduced only slightly in the rec10-155 mutant. Recently Ellermeier and Smith (2005) observed much greater levels of reduction in inter-and intragenic recombination at all loci/intervals tested with a rec10 null mutant (rec10-175; $40-fold in all cases). This includes loci at which we observed only relatively minor reductions.…”

Interactions between Mei4, Rec114, and other proteins required for meiotic DNA double-strand break formation in Saccharomyces cerevisiae

“…The potential Rec114 ortholog in S. pombe, Rec7, also localizes to chromosomes, but Rec7 foci appear closely associated with chromosome axes and these foci do not form in mutants defective for the axis-associated protein Rec10 (Lorenz et al 2006). These differences may reflect the closer functional dependency between DSB formation and the cohesin-containing axes in S. pombe (Ellermeier and Smith 2005;Loidl 2006;Lorenz et al 2006;Wells et al 2006). …”