title: The Landscape of Mouse Meiotic Double-Strand Break Formation, Processing, and Repair.
abstract: Heritability and genome stability are shaped by meiotic recombination, which is initiated via hundreds of DNA double-strand breaks (DSBs). The distribution of DSBs throughout the genome is not random, but mechanisms molding this landscape remain poorly understood. Here, we exploit genome-wide maps of mouse DSBs at unprecedented nucleotide resolution to uncover previously invisible spatial features of recombination. At fine scale, we reveal a stereotyped hotspot structure-DSBs occur within narrow zones between methylated nucleosomes-and identify relationships between SPO11, chromatin, and the histone methyltransferase PRDM9. At large scale, DSB formation is suppressed on non-homologous portions of the sex chromosomes via the DSB-responsive kinase ATM, which also shapes the autosomal DSB landscape at multiple size scales. We also provide a genome-wide analysis of exonucleolytic DSB resection lengths and elucidate spatial relationships between DSBs and recombination products. Our results paint a comprehensive picture of features governing successive steps in mammalian meiotic recombination.
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Lange
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Memorial Sloan Kettering Cancer Center, Howard Hughes Medical Institute, New York, NY 10065, USA.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Tri-Institutional Training Program in Computational Biology and Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Sam E
authors.initials: SE
authors.lastname: Tischfield
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Seoyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.affiliation: Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: m-jasin@ski.mskcc.org.
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Memorial Sloan Kettering Cancer Center, Howard Hughes Medical Institute, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA. Electronic address: s-keeney@ski.mskcc.org.
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D019175:DNA Methylation; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009707:Nucleosomes / Q000201:enzymology / Q000235:genetics; D014960:X Chromosome / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D002843:Chromatin; D004706:Endodeoxyribonucleases; D011495:Histone-Lysine N-Methyltransferase; D009707:Nucleosomes; D000099257:Meiotic Recombination Protein SPO11; C534829:prdm9 protein, mouse; C576325:Atm protein, mouse
keywords: DNA damage; DNA repair; PRDM9; SPO11; chromatin; double-strand break; homologous recombination; meiosis; mouse; resection