The TopoVIB-Like protein family is required for meiotic DNA double-strand break formation

作者：Thomas Robert, Alexandre Nore, Christine Brun, C. Maffre, Barbara Crimi, Vincent Guichard, Henri Marc Bourbon, Bernard de Massy · 发表于：Science · 年份：2016 · DOI：10.1126/science.aad5309 · 被引用次数：318 · 研究领域：DNA Repair Mechanisms、Polyomavirus and related diseases、Acute Lymphoblastic Leukemia research

Meiotic recombination is induced by the formation of DNA double-strand breaks (DSBs) catalyzed by SPO11, the ortholog of subunit A of TopoVI DNA topoisomerase (TopoVIA). TopoVI activity requires the interaction between A and B subunits. We identified a conserved family of plant and animal proteins [the TOPOVIB-Like (TOPOVIBL) family] that share strong structural similarity to the TopoVIB subunit of TopoVI DNA topoisomerase. We further characterize the meiotic recombination proteins Rec102 (Saccharomyces cerevisiae), Rec6 (Schizosaccharomyces pombe), and MEI-P22 (Drosophila melanogaster) as homologs to the transducer domain of TopoVIB. We demonstrate that the mouse TOPOVIBL protein interacts and forms a complex with SPO11 and is required for meiotic DSB formation. We conclude that meiotic DSBs are catalyzed by a complex involving SPO11 and TOPOVIBL.