Topoisomerases modulate the timing of meiotic DNA breakage and chromosome morphogenesis in Saccharomyces cerevisiae

Abstract

AbstractDuring meiotic prophase, concurrent transcription, recombination, and chromosome synapsis, place substantial topological strain on chromosomal DNA, but the role of topoisomerases in this context remains poorly defined. Here, we analyzed the roles topoisomerases I and II (Top1 and Top2) during meiotic prophase in Saccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes. Enrichment partially overlaps meiotic double-strand break (DSB) hotspots, but disruption of either topoisomerase has different effects during meiotic recombination. TOP1 disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive top2-1 mutants accumulate DSBs on synapsed chromosomes and exhibit a marked delay in meiotic chromosome remodeling. This defect results from a delay in recruiting the meiotic chromosome remodeler Pch2/TRIP13 but, unexpectedly, is not due to a loss of Top2 catalytic activity. Instead, mutant Top2-1 protein has reduced contact with chromatin but remains associated with meiotic chromosomes, and we provide evidence that this altered binding is responsible for the delay in chromosome remodeling. Our results imply independent roles for topoisomerases I and II in modulating meiotic recombination.