Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination |
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Authors: | Panizza Silvia Mendoza Marco A Berlinger Marc Huang Lingzhi Nicolas Alain Shirahige Katsuhiko Klein Franz |
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Institution: | 1 Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 1, A-1030 Vienna, Austria 2 Recombinaison et Instabilité Génétique, Institut Curie Centre de Recherche, Centre National de la Recherche Scientifique UMR3244, Université Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France 3 Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan |
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Abstract: | Meiotic recombination between homologous chromosomes initiates via programmed DNA double-strand breaks (DSBs), generated by complexes comprising Spo11 transesterase plus accessory proteins. DSBs arise concomitantly with the development of axial chromosome structures, where the coalescence of axis sites produces linear arrays of chromatin loops. Recombining DNA sequences map to loops, but are ultimately tethered to the underlying axis. How and when such tethering occurs is currently unclear. Using ChIPchip in yeast, we show that Spo11-accessory proteins Rec114, Mer2, and Mei4 stably interact with chromosome axis sequences, upon phosphorylation of Mer2 by S phase Cdk. This axis tethering requires meiotic axis components (Red1/Hop1) and is modulated in?a domain-specific fashion by cohesin. Loss of Rec114, Mer2, and Mei4 binding correlates with loss of DSBs. Our results strongly suggest that hotspot sequences become tethered to axis sites by the DSB machinery prior to DSB formation. |
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