title: Replication origin selection regulates the distribution of meiotic recombination.
abstract: The program of DNA replication, defined by the temporal and spatial pattern of origin activation, is altered during development and in cancers. However, whether changes in origin usage play a role in regulating specific biological processes remains unknown. We investigated the consequences of modifying origin selection on meiosis in fission yeast. Genome-wide changes in the replication program of premeiotic S phase do not affect meiotic progression, indicating that meiosis neither activates nor requires a particular origin pattern. In contrast, local changes in origin efficiencies between different replication programs lead to changes in Rad51 recombination factor binding and recombination frequencies in these domains. We observed similar results for Rad51 when changes in efficiencies were generated by directly targeting expression of the Cdc45 replication factor. We conclude that origin selection is a key determinant for organizing meiotic recombination, providing evidence that genome-wide modifications in replication program can modulate cellular physiology.
authors.affiliation: Institute of Genetics and Development of Rennes, CNRS UMR 6290, 2 Avenue du Pr. Léon Bernard, 35043 Rennes, France; The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. Electronic address: pei-yun.wu@univ-rennes1.fr.
authors.forename: Pei-Yun Jenny
authors.initials: PY
authors.lastname: Wu
authors.affiliation: The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA; The Francis Crick Institute, 215 Euston Road, London NW12BE, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Nurse
mesh_terms: D002453:Cell Cycle; D047369:Chromatin Immunoprecipitation; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D008540:Meiosis; D009687:Nuclear Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D051135:Rad51 Recombinase / Q000378:metabolism*; D011995:Recombination, Genetic; D018741:Replication Origin; D016196:S Phase; D012568:Schizosaccharomyces / Q000235:genetics* / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C116395:CDC45 protein, S pombe; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C084232:RHP51 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D051135:Rad51 Recombinase