4.4 Article

Topoisomerases Modulate the Timing of Meiotic DNA Breakage and Chromosome Morphogenesis in Saccharomyces cerevisiae

Journal

GENETICS
Volume 215, Issue 1, Pages 59-73

Publisher

GENETICS SOCIETY AMERICA
DOI: 10.1534/genetics.120.303060

Keywords

Meiosis; topo I; topo II; synaptonemal complex; Hop1

Funding

  1. National Institutes of Health [GM-111715, GM-123035]

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Meiotic chromosomes experience substantial strain due to morphological changes and ongoing metabolism of the DNA. Outside of meiosis, topology-modifying enzymes called topoisomerases manage this sort of strain, but their function during meiotic prophase has not been thoroughly explored... During 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 of topoisomerases I and II ( and ) during meiotic prophase in Saccharomyces cerevisiae. We show that both topoisomerases accumulate primarily in promoter-containing intergenic regions of actively transcribing genes, including many meiotic double-strand break (DSB) hotspots. Despite the comparable binding patterns, and mutations have different effects on meiotic recombination. disruption delays DSB induction and shortens the window of DSB accumulation by an unknown mechanism. By contrast, temperature-sensitive -1 mutants exhibit a marked delay in meiotic chromosome remodeling and elevated DSB signals on synapsed chromosomes. The problems in chromosome remodeling were linked to altered binding patterns rather than a loss of catalytic activity, and stemmed from a defect in recruiting the chromosome remodeler /TRIP13 to synapsed chromosomes. No chromosomal defects were observed in the absence of . Our results imply independent roles for and in modulating meiotic chromosome structure and recombination.

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