1. Chromosomes and Gene Expression
  2. Microbiology and Infectious Disease
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Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation

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Cite this article as: eLife 2016;5:e12765 doi: 10.7554/eLife.12765

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.

Article and author information

Author details

  1. Rebecca Devlin

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Catarina A Marques

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Daniel Paape

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Marko Prorocic

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrea C Zurita-Leal

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Samantha J Campbell

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Craig Lapsley

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Nicholas Dickens

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Richard McCulloch

    The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    For correspondence
    Richard.McCulloch@glasgow.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Nina Papavasiliou, Rockefeller University, United States

Publication history

  1. Received: November 2, 2015
  2. Accepted: May 26, 2016
  3. Accepted Manuscript published: May 26, 2016 (version 1)
  4. Version of Record published: July 15, 2016 (version 2)

Copyright

© 2016, Devlin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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