Mer3 helicase protects early crossover intermediates from STR complex disassembly during meiosis

Abstract

During meiosis I it is necessary that homologous chromosomes are linked to one another so that they can be faithfully separated. S. cerevisiae Mer3 (HFM1 in mammals) is a SF2 helicase and member of the ZMM group of proteins, that facilitates the formation of class I crossovers during meiosis. Here we describe the structural organisation of Mer3 and, using AlphaFold modelling and XL-MS, we further characterise the previously described interaction with Mlh1-Mlh2. We find that Mer3 also forms a previously undescribed complex with the recombination regulating factors Top3 and Rmi1 and that this interaction is competitive with Sgs1BLM helicase in a phospho-dependent manner. Using in vitro reconstituted D-loop assays we show that Mer3 inhibits the anti-recombination activity of Sgs1/Top3/Rmi1 (STR) complex. Thus we provide a mechanism whereby Mer3 downregulates the anti-crossover activity of the STR complex, hence promoting the formation of crossovers during meiosis I.