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Abstract

Meiosis is a key step in sexual reproduction, which leads to the for- mation of haploid gametes from a diploid cell. During genome reduction, the homologous chromosomes are segregated into daughter cells, therefore they have to be physically linked via homologous recombination. The linkage is enabled by repair of programmed double-stranded DNA breaks (DSBs) using the homologous chromosome instead of the sister chromatid. Forma- tion of DSB has to be strictly controlled - too little breaks would not be sufficient to hold homologs together, too many breaks would lead to chromosome destabilization. It is known that DSB formation in S. cerevisiae involves regulation by phosphorylation and the assembly and disassembly of the Hop1-Red1-Mek1- and Rec114-Mer2-Mei4-complexes together with the nucleosome bind- ing protein Spp1. However, mechanistic detail of these processes are lacking. We use an in vitro reconstitution approach combining biochemistry and structural biology to provide insight into the mechanisms underlying DSB control; both in time and in space. Unravelling DSB control would represent a significant step for- ward in our understanding of break positioning, genome stability and, ultimately, the critical process of meiosis as a whole.