A Hierarchical Combination of Factors Shapes the Genome-wide Topography of Yeast Meiotic Recombination Initiation

SummaryThe nonrandom distribution of meiotic recombination influences patterns of inheritance and genome evolution, but chromosomal features governing this distribution are poorly understood. Formation of the DNA double-strand breaks (DSBs) that initiate recombination results in the accumulation of Spo11 protein covalently bound to small DNA fragments. By sequencing these fragments, we uncover a genome-wide DSB map of unprecedented resolution and sensitivity. We use this map to explore how DSB distribution is influenced by large-scale chromosome structures, chromatin, transcription factors, and local sequence composition. Our analysis offers mechanistic insight into DSB formation and early processing steps, supporting the view that the recombination terrain is molded by combinatorial and hierarchical interaction of factors that work on widely different size scales. This map illuminates the occurrence of DSBs in repetitive DNA elements, repair of which can lead to chromosomal rearrangements. We also discuss implications for evolutionary dynamics of recombination hot spots.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (285 K)Download as PowerPoint slideHighlights► High-resolution view of meiotic DNA breaks from deep sequencing of Spo11-bound oligos ► Landscape of dsDNA breaks reflects large- and small-scale chromosome features ► Hot spots are just one level of spatial organization of meiotic recombination ► dsDNA breaks occur frequently in repetitive DNA, a risk for chromosome rearrangement