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Deconstructing the meiotic (yeast) chromosome


Principal Investigator: Franz Klein

We study meiotic recombination and chromosome segregation in S. cerevisiae as model organism, to understand the interplay between chromosome structure and recombination. During meiosis, the genetic content of a diploid cell is reduced to half, a prerequisite for the production of gametes and for sexual reproduction. Our experience shows, that the important processes are conserved between yeast and man, so that many of our findings can be generalized.

Aim of this study
Data from our lab and others define the structure of yeast chromosomes in detail. One way to view the result is to understand the chromosome as a modular structure. Here we attempt to define modules important for recombination. Axis regions are essential for recombination initiation at loop sites. We aim to define axis modules, DSB modules and study them isolated and in combination with other chromosomal landmarks. Thus the role of transcription, replication, the centromere, cohesion loading and others in recombination can be evaluated with precision.
Technically the project(s) utilize fast YAC construction using yeast recombineering and in vivo chromosome bi-section by induced recombination. The readouts will be protein-DNA interaction in vivo and DSB formation.

ChIPseq profile

The red Chipseq-profile depicts the chromosome association of Red1 axis protein, which is crucial for initiation of recombination during meiosis. The blue bars map the chromosomal positions, at which recombination is initiated by DNA breaks on “loops”, alternating with Red1 sites (axis sites). Below is an abstract view of the same chromosome, where axis and DSB sites are imagined as modules. In the bottom row constructs are listed, which will be tested for their abilities to establish an axis and form DSBs. (YCP-yeast centromere plasmid, YAC-yeast artificial chromosome)