title: Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation.
abstract: Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating - a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility.
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Devlin
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Catarina A
authors.identifier: 0000-0003-1324-5448
authors.initials: CA
authors.lastname: Marques
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Paape
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Marko
authors.initials: M
authors.lastname: Prorocic
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Zurita-Leal
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Campbell
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Craig
authors.initials: C
authors.lastname: Lapsley
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dickens
authors.affiliation: The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Richard
authors.identifier: 0000-0001-5739-976X
authors.initials: R
authors.lastname: McCulloch
mesh_terms: D000940:Antigenic Variation; D053960:DNA Breaks; D004260:DNA Repair; D004261:DNA Replication; D053484:RecQ Helicases / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000378:metabolism*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000096:biosynthesis*
chemical_list: D014643:Variant Surface Glycoproteins, Trypanosoma; D053484:RecQ Helicases
keywords: DNA break; DNA repair; DNA replication; Trypanosoma; Variant Surface Glycoprotein; antigenic variation; chromosomes; genes; infectious disease; microbiology