title: Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major.
abstract: Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs). Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance.
authors.affiliation: Functional Organization of the Genome Group, Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lombraña
authors.affiliation: Functional Organization of the Genome Group, Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Álvarez
authors.affiliation: Functional Organization of the Genome Group, Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Fernández-Justel
authors.affiliation: Functional Organization of the Genome Group, Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Almeida
authors.affiliation: Functional Organization of the Genome Group, Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Poza-Carrión
authors.affiliation: Centro Nacional de Biotecnología (CSIC), Darwin 3, 28049 Madrid, Spain.
authors.forename: Fábia
authors.initials: F
authors.lastname: Gomes
authors.affiliation: Centro Nacional de Biotecnología (CSIC), Darwin 3, 28049 Madrid, Spain.
authors.forename: Arturo
authors.initials: A
authors.lastname: Calzada
authors.affiliation: Functional Organization of the Genome Group, Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Requena
authors.affiliation: Functional Organization of the Genome Group, Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Nicolás Cabrera 1, 28049 Madrid, Spain. Electronic address: mgomez@cbm.csic.es.
authors.forename: María
authors.initials: M
authors.lastname: Gómez
mesh_terms: D000818:Animals; D002843:Chromatin / Q000469:parasitology*; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics*; D042522:DNA Replication Timing / Q000235:genetics; D005057:Eukaryotic Cells / Q000469:parasitology; D006801:Humans; D018320:Leishmania major / Q000235:genetics*; D009707:Nucleosomes / Q000469:parasitology; D010271:Parasites / Q000235:genetics; D018741:Replication Origin / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D004247:DNA
keywords: DNA replication origins; Leishmania major; genome-wide mapping; nucleosomes; replication timing; transcription