Protein Determinants of Meiotic DNA Break Hot Spots

Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to hundreds of times more frequently at special sites, called hot spots, than in other regions of the genome. What distinguishes hot spots from cold regions is an unsolved problem, although transcription factors determine some hot spots. We report the discovery that three coiled-coil proteins-Rec25, Rec27, and Mug20-bind essentially all hot spots with great specificity even without DSB formation. These small proteins are components of linear elements, are related to synaptonemal complex proteins, and are essential for nearly all DSBs at most hot spots. Our results indicate these hot spot determinants activate or stabilize the DSB-forming protein Rec12 (Spoil homolog) rather than promote its binding to hot spots. We propose a paradigm for hot spot determination and crossover control by linear element proteins.