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Spo11-oligo mapping in S. cerevisiae Ctf19/CCAN kinetochore sub-complex mutant mcm21

ABSTRACT: During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE72683 | GEO | 2015/12/15

SECONDARY ACCESSION(S): PRJNA294661

REPOSITORIES: GEO

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Spo11-oligo mapping in S. cerevisiae Ctf19/CCAN kinetochore sub-complex mutant mcm21

Project description:During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes. Two samples total: two biological replicate Spo11-oligo maps of S. cerevisiae SK1 mcm21 null mutant

2015-12-15 | E-GEOD-72683 | biostudies-arrayexpress

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Project description:In meiosis, an excess number of DNA double-strand breaks (DSBs), the initiating DNA lesion, is formed compared to the number of crossovers, one of their repair products that creates the physical links between homologs and allows their correct segregation. It is not known if all DSB hotspots are also crossover hotspots, or if the ratio between DSB and crossovers varies with the chromosomal location. Here, to systematically investigate variation in the DSB/crossover ratio, we have established the genome-wide map of the Zip3 protein binding sites in budding yeast meiosis. We show that Zip3 associates with DSB sites when these are engaged into repair by crossing over, and that Zip3 binding frequency at DSB reflects its tendency to be repaired as a crossover. We further show that the relative amount of Zip3 per DSB varies with the chromosomal location and identify chromosomal features associated with high or low Zip3 per DSB ratio. Among these is the negative regulation by proximity to a centromere and positive by the proximity to axis-associated sequences. This work opens interesting perspectives to understand the role of these extra DSB that are not frequently used for crossover and our findings may extend to mammals that have a large excess of DSB compared to crossovers.

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