title: Mouse tetrad analysis provides insights into recombination mechanisms and hotspot evolutionary dynamics.
abstract: The ability to examine all chromatids from a single meiosis in yeast tetrads has been indispensable for defining the mechanisms of homologous recombination initiated by DNA double-strand breaks (DSBs). Using a broadly applicable strategy for the analysis of chromatids from a single meiosis at two recombination hotspots in mouse oocytes and spermatocytes, we demonstrate here the unidirectional transfer of information-gene conversion-in both crossovers and noncrossovers. Whereas gene conversion in crossovers is associated with reciprocal exchange, the unbroken chromatid is not altered in noncrossover gene conversion events, providing strong evidence that noncrossovers arise from a distinct pathway. Gene conversion frequently spares the binding site of the hotspot-specifying protein PRDM9, with the result that erosion of the hotspot is slowed. Thus, mouse tetrad analysis demonstrates how unique aspects of mammalian recombination mechanisms shape hotspot evolutionary dynamics.
authors.affiliation: 1] Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, Texas, USA. [3].
authors.forename: Francesca
authors.initials: F
authors.lastname: Cole
authors.affiliation: 1] Institut de Génétique Humaine, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Montpellier, France. [2].
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baudat
authors.affiliation: Institut de Génétique Humaine, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Montpellier, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Grey
authors.affiliation: 1] Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
authors.affiliation: Institut de Génétique Humaine, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: de Massy
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
mesh_terms: D000818:Animals; D026501:Blotting, Southwestern; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism; D003434:Crossing Over, Genetic; D019143:Evolution, Molecular; D005260:Female; D005785:Gene Conversion; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D011995:Recombination, Genetic / Q000235:genetics*; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D011495:Histone-Lysine N-Methyltransferase; C534829:prdm9 protein, mouse