Mutational analysis of Mei5, a subunit of Mei5-Sae3 complex, in Dmc1-mediated recombination during yeast meiosis.

Interhomolog recombination in meiosis is mediated by the Dmc1 recombinase. The Mei5-Sae3 complex of Saccharomyces cerevisiae promotes Dmc1 assembly and functions with Dmc1 for homology-mediated repair of meiotic DNA double-strand breaks. How Mei5-Sae3 facilitates Dmc1 assembly remains poorly understood.

The role of conserved amino acid residues of Sae3 in Mei5-Sae3 complex for Dmc1 assembly in meiotic recombination.

Meiotic recombination between homologous chromosomes is promoted by the collaborative action of two RecA homologs, Rad51 and meiosis-specific Dmc1. The filament assembly of Dmc1 is promoted by meiosis-specific Mei5-Sae3 in budding yeast. Mei5-Sae3 shows sequence similarity to fission yeast Sfr1-Swi5, which stimulates DNA strand exchanges by Rad51 as well as Dmc1.

Design and Synthesis of Styrenylcyclopropylamine LSD1 Inhibitors.

Leveraging the catalytic machinery of LSD1 (KDM1A), a series of covalent styrenylcyclopropane LSD1 inhibitors were identified. These inhibitors represent a new class of mechanism-based inhibitors that target and covalently label the FAD cofactor of LSD1. The series was rapidly progressed to potent biochemical and cellular LSD1 inhibitors with good physical properties.