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Abstract:
Meiosis is a specialised form of cell division that results in the generation of haploid gametes. During meiosis I, it is essential that homologous chromosomes be linked in order that they be properly segregated. Linkages are generated through crossovers, arising from recombination mediated repair of double-stranded DNA breaks (DSBs). Meiotic DSBs are non-random, instead they arise through the control of the conserved topoisomerase Spo11 and its chromosome associated cofactors. In the budding yeast S. cerevisiae, Mer2 is a Spo11-associated factor. Using recombinant proteins and synthetic nucleosomes, combined with hybrid structural biology and biochemistry we extensively characterise Mer2. We discover several novel and unexpected interactions that provide exciting insights into the regulation of Spo11, and the formation of meiotic DSBs. Once DSBs are formed they are resected to ssDNA and enter into the homologous recombination (HR) pathway. In meiosis the homologous chromosome is used as a template. A number of factors bias the formation of crossovers from nascent HR repair intermediates. We discover that the helicase Mer3, protects “D-loop” repair intermediates by antagonising the anti-crossover factor Sgs1. Taken together, our in vitro efforts have provided much needed clarity on the initiation of meiotic recombination, its regulation, and on how the normally deleterious formation of crossovers is acilitated.
