A unique aspect of meiosis is the segregation of homologous chromosomes at the meiosis I division. Homologs are physically connected prior to segregation by crossing over between nonsister chromatids. Crossovers arise from the repair of induced double-strand breaks (DSBs). In many organisms, more DSBs are formed than crossovers in a given nucleus. It has been previously suggested that repair of DSBs to noncrossover recombination products aids homolog alignment. Here we explore how two modes of the meiotic recombination pathway (crossover and noncrossover) and meiotic telomere reorganization contribute to the pairing and close juxtaposition of homologous chromosomes in budding yeast. We found that intermediates in the DSB repair pathway leading to both crossover and noncrossover recombination products contribute independently to close, stable homolog juxtaposition (CSHJ), a measurable state of homolog pairing. Analysis of the ndj1⌬ mutant indicates that the effect of meiotic telomere reorganization on CSHJ is exerted through recombination intermediates at interstitial chromosomal loci, perhaps through the noncrossover branch of the DSB repair pathway. We suggest that transient, early DSB-initiated interactions, including those that give rise to noncrossovers, are important for homolog recognition and juxtaposition.[Keywords: Homolog; meiosis; pairing; recombination; telomeres]Received December 28, 2004; revised version accepted February 15, 2005. Meiosis is the process in which a parent diploid cell undergoes two rounds of chromosome segregation, after one round of replication, to yield four haploid gametes. A universal component of meiosis I is the reductional segregation of homologous chromosomes. Nondisjunction, or improper segregation of homologs, at this stage can lead to gamete aneuploidy. Three factors contribute to the tension required for the reductional segregation of homologs at anaphase I in most organisms: (1) crossing over between homologous chromosomes, (2) cohesion between sister chromatids, and (3) monopolar spindle attachment of sister chromatids at metaphase (Page and Hawley 2003).Crossing over involves the reciprocal exchange of chromosome arms and can be visualized at late stages of meiotic prophase as chiasmata. Such exchange events are a manifestation of double-strand break (DSB)-promoted homologous recombination. Formation and repair of meiotically induced DSBs involve both DSB repair enzymes and meiosis-specific factors (for reviews, see Zickler and Kleckner 1999;Keeney 2001). Meiosis-specific factors bias recombination between homologous chromosomes instead of sister chromatids (Schwacha and Kleckner 1997) and ensure that at least one crossover occurs between every homolog pair (for review, see Bishop and Zickler 2004).A key event in crossover formation is the recognition and pairing of homologous chromosomes. An outstanding question is what brings homologs together in meiosis. Is it early molecular events, late-forming molecules in which homologs are clearly linked by chemical or hyd...

A unique aspect of meiosis is the segregation of homologous chromosomes at the meiosis I division. The pairing of homologous chromosomes is a critical aspect of meiotic prophase I that aids proper disjunction at anaphase I. We have used a site-specific recombination assay in Saccharomyces cerevisiae to examine allelic interaction levels during meiosis in a series of mutants defective in recombination, chromatin structure, or intracellular movement. Red1, a component of the chromosome axis, and Mnd1, a chromosome-binding protein that facilitates interhomolog interaction, are critical for achieving high levels of allelic interaction. Homologous recombination factors (Sae2, Rdh54, Rad54, Rad55, Rad51, Sgs1) aid in varying degrees in promoting allelic interactions, while the Srs2 helicase appears to play no appreciable role. Ris1 (a SWI2/ SNF2 related protein) and Dot1 (a histone methyltransferase) appear to play minor roles. Surprisingly, factors involved in microtubule-mediated intracellular movement (Tub3, Dhc1, and Mlp2) appear to play no appreciable role in homolog juxtaposition, unlike their counterparts in fission yeast. Taken together, these results support the notion that meiotic recombination plays a major role in the high levels of homolog interaction observed during budding yeast meiosis.M EIOSIS is the process by which a parent diploid cell undergoes one round of DNA replication followed by two rounds of chromosome segregation to yield haploid gametes. A unique aspect of meiosis is the segregation of homologous chromosomes at the first meiotic division. Nondisjunction, or improper segregation of homologs, at this stage can lead to gamete aneuploidy, which is a major cause of birth defects in humans (Hassold and Hunt 2001). Homologs are able to correctly orient toward opposite poles of the meiosis I spindle, because a collaboration of DNA crossovers (CR) with sister-chromatid cohesion forms temporary connections between the homologs (Page and Hawley 2003;Petronczki et al. 2003).Homologous chromosomes form progressively stronger associations as cells proceed through meiotic prophase I (Zickler and Kleckner 1999;Storlazzi et al. 2003). In the budding yeast, plants, and mammals, transacting factors required for meiotic recombination are crucial for the pairing and crossing over between homologous chromosomes. In contrast, synaptonemal complex (SC) formation, meiotic nuclear reorganization, and an achiasmate segregation system appear to play supplementary roles in meiotic homolog pairing in the budding yeast (Loidl et al.