Abstract
To segregate accurately during meiosis in most species, homologous chromosomes must recombine1. Small chromosomes would risk missegregation if recombination were randomly distributed, so the double-strand breaks (DSBs) initiating recombination are not haphazard2. How this nonrandomness is controlled is not understood, although several pathways ensuring that DSBs occur at the appropriate time, number, and place are known. Meiotic DSBs are made by Spo11 and accessory “DSB proteins,” including Rec114 and Mer2, which assemble on chromosomes3–7 and are nearly universal in eukaryotes8–11. Here we demonstrate how Saccharomyces cerevisiae integrates multiple temporally distinct pathways to regulate chromosomal binding of Rec114 and Mer2, thereby controlling the duration of a DSB-competent state. Engagement of homologous chromosomes with one another regulates the dissociation of Rec114/Mer2 later in prophase I, whereas replication timing and proximity to centromeres or telomeres influence Rec114/Mer2 accumulation early. Another early mechanism boosts Rec114/Mer2 binding specifically on the shortest chromosomes, subject to selection pressure to maintain hyperrecombinogenic properties of these chromosomes. Thus, an organism’s karyotype and risk of meiotic missegregation influence the shape and evolution of its recombination landscape. Our results create a cohesive view of a multifaceted and evolutionarily constrained system that ensures DSB allocation to all pairs of homologous chromosomes.
Highlights
A critical goal in meiotic prophase is to allocate crossovers to all pairs of homologous chromosomes to ensure proper segregation in the first meiotic division (MI) (Page and Hawley, 2003)
We show that a separable mechanism allows the shortest chromosomes to quickly accumulate especially high levels of double-strand breaks (DSBs) proteins, and we provide evidence that selective pressure maintains this property of little chromosomes over evolutionary time scales
To understand how DSB proteins associate with meiotic chromatin, we performed chromatin immunoprecipitation (ChIP)-seq for Rec114 or Mer2 at multiple time points from three synchronized meiotic cultures and calibrated coverage maps by quantitative PCR (qPCR (Murakami and Keeney, 2014)) (Figures 1C and 1D)
Summary
A critical goal in meiotic prophase is to allocate crossovers to all pairs of homologous chromosomes to ensure proper segregation in the first meiotic division (MI) (Page and Hawley, 2003). DSB formation requires topoisomerase-like Spo and nine accessory proteins (“DSB proteins,” including Rec114 and Mer2), which interact with each other and assemble complexes on meiotic chromosomes (Arora et al, 2004; Li et al, 2006; Maleki et al, 2007; Panizza et al, 2011). Most of these factors are nearly universal in eukaryotes, including fission yeast (Miyoshi et al, 2012) and mammals (Kumar et al, 2010; Robert et al, 2016; Stanzione et al, 2016; Tesse et al, 2017)
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