title: Evolutionarily diverse determinants of meiotic DNA break and recombination landscapes across the genome.
abstract: Fission yeast Rec12 (Spo11 homolog) initiates meiotic recombination by forming developmentally programmed DNA double-strand breaks (DSBs). DSB distributions influence patterns of heredity and genome evolution, but the basis of the highly nonrandom choice of Rec12 cleavage sites is poorly understood, largely because available maps are of relatively low resolution and sensitivity. Here, we determined DSBs genome-wide at near-nucleotide resolution by sequencing the oligonucleotides attached to Rec12 following DNA cleavage. The single oligonucleotide size class allowed us to deeply sample all break events. We find strong evidence across the genome for differential DSB repair accounting for crossover invariance (constant cM/kb in spite of DSB hotspots). Surprisingly, about half of all crossovers occur in regions where DSBs occur at low frequency and are widely dispersed in location from cell to cell. These previously undetected, low-level DSBs thus play an outsized and crucial role in meiosis. We further find that the influence of underlying nucleotide sequence and chromosomal architecture differs in multiple ways from that in budding yeast. DSBs are not strongly restricted to nucleosome-depleted regions, as they are in budding yeast, but are nevertheless spatially influenced by chromatin structure. Our analyses demonstrate that evolutionarily fluid factors contribute to crossover initiation and regulation.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA;
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Fowler
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10065, USA;
authors.forename: Mariko
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA;
authors.forename: Neta
authors.initials: N
authors.lastname: Milman
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10065, USA; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA gsmith@fhcrc.org s-keeney@ski.mskcc.org.
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; gsmith@fhcrc.org s-keeney@ski.mskcc.org.
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Smith
mesh_terms: D002843:Chromatin / Q000378:metabolism; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D019143:Evolution, Molecular; D016681:Genome, Fungal; D008540:Meiosis; D008957:Models, Genetic; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D002843:Chromatin; D029702:Schizosaccharomyces pombe Proteins