In eukaryotic cells, cohesion between sister chromatids allows chromosomes to biorient on the metaphase plate and holds them together until they separate into daughter cells during mitosis. Cohesion is mediated by the cohesin protein complex. Although the association of this complex with particular regions of the genome is highly reproducible, it is unclear what distinguishes a chromosomal region for cohesin association. Since one of the primary locations of cohesin is intergenic regions between converging transcription units, we explored the relationship between transcription and cohesin localization. Chromatin immunoprecipitation followed by hybridization to a microarray (ChIP chip) indicated that transcript elongation into cohesin association sites results in the local disassociation of cohesin. Once transcription is halted, cohesin can reassociate with its original sites, independent of DNA replication and the cohesin loading factor Scc2, although cohesin association with chromosomes in G 2 /M is not functional for cohesion. A computer program was developed to systematically identify differences between two ChIP chip data sets. Our results are consistent with a model for cohesin association in which (i) a portion of cohesin can be dynamically loaded and unloaded to accommodate transcription and (ii) the cohesin complex has preferences for features of chromatin that are a reflection of the local transcriptional status. Taken together, our results suggest that cohesion may be degraded by transcription.Dividing cells must ensure that their chromosomes are copied exactly once and that new cells receive exactly a single copy of each chromosome. Failure to do so can result in aneuploidy, an abnormal number of chromosomes that typically leads to developmental abnormalities or cell death. During DNA replication, sister chromatids are cohered and cohesion is maintained until the metaphase-to-anaphase transition (28, 42). Sister chromatid cohesion facilitates the biorientation of chromosomes along the metaphase spindle and resists the tendency of microtubules to prematurely separate chromosomes once bipolar attachments are established (38). Cohesin also contributes to DNA repair (37, 44) and condensation (15).In eukaryotic cells, cohesion is mediated by several evolutionarily conserved proteins. The complex itself is composed of two SMC (structural maintenance of chromosomes) subunits, Smc1 and Smc3, and two non-SMC subunits, Mcd1/Scc1 and Scc3. Together, these subunits form a large ring-shaped complex that is essential for cohesion between sister chromatids (14, 16). The loading of cohesin onto chromosomes in G 1 is dependent on the Scc2/4 complex (5, 40). Cohesion is established during DNA replication (42). Cohesion is dissolved at the metaphase-to-anaphase transition by separase, which cleaves Mcd1, resulting in the movement of sister chromatids into separate daughter cells (41,43). Although the molecular structure of cohesin has been well studied, exactly how this ring-shaped complex interacts with DNA remains unc...

During meiosis, each chromosome must pair with its homolog and undergo meiotic crossover recombination in order to segregate properly at the first meiotic division. Recombination in meiosis in Saccharomyces cerevisiae relies on two Escherichia coli recA homologs, Rad51 and Dmc1, as well as the more recently discovered heterodimer Mnd1/Hop2. Meiotic recombination in S. cerevisiae mnd1 and hop2 single mutants is initiated via double-strand breaks (DSBs) but does not progress beyond this stage; heteroduplex DNA, joint molecules, and crossovers are not detected. Whereas hop2 and mnd1 single mutants are profoundly recombination defective, we show that mnd1 rad51, hop2 rad51, and mnd1 rad17 double mutants are able to carry out crossover recombination. Interestingly, noncrossover recombination is absent, indicating a role for Mnd1/Hop2 in the designation of DSBs for noncrossover recombination. We demonstrate that in the rad51 mnd1 double mutant, recombination is more likely to occur between repetitive sequences on nonhomologous chromosomes. Our results support a model in which Mnd1/Hop2 is required for DNA-DNA interactions that help ensure Dmc1-mediated stable strand invasion between homologous chromosomes, thereby preserving genomic integrity.Sexually reproducing organisms have a specialized developmental pathway for gametogenesis in which diploid cells undergo meiosis to produce haploid germ cells. Prior to the first meiotic division, homologs are replicated, paired, and recombined. In the first meiotic division, homologs segregate and in the second meiotic division, sisters segregate. Recombination serves at least three purposes: (i) damage to homologs can be repaired, (ii) diversity is generated for subsequent generations, and (iii) proper chromosome segregation is facilitated.During meiosis, homologous chromosomes interact via recombination to produce at least one crossover (CO) per chromosome in order to segregate properly at the first nuclear division. Meiotic recombination begins with double-strand breaks (DSBs) made by the Spo11 endonuclease (4, 26). The 5Ј ends of these breaks are resected. As shown in yeast, the majority of COs arise via single end invasions which are the result of a 3Ј single-stranded DNA end invading a homologous chromosome (23). As recombination progresses, joint molecules (JM) can be detected which are the result of the invading 3Ј end being extended by DNA polymerization and then recaptured, creating a double Holliday junction that contains heteroduplex DNA (2, 39). For each double Holliday junction, resolution is required for the completion of CO recombination and proper chromosome separation at the first meiotic division. DSBs can also give rise to noncrossovers (NCOs) which arise via other intermediates which remain to be defined (1, 23). In yeast, DSBs are likely marked to become NCOs or COs prior to or concomitant with stable strand invasion (8, 9).In order for homologous recombination to occur, homologous sequences must find each other. Homologous recombination between allelic pos...