1. Genetics and Genomics
  2. Microbiology and Infectious Disease

Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication

  1. Jeziel Dener Damasceno  Is a corresponding author
  2. Catarina A Marques
  3. Dario Beraldi
  4. Kathryn Crouch
  5. Craig Lapsley
  6. Ricardo Obonaga
  7. Luiz R O Tosi
  8. Richard McCulloch  Is a corresponding author
  1. University of Glasgow, United Kingdom
  2. University of São Paulo, Brazil
https://doi.org/10.7554/eLife.58030
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Cite this article
  1. Jeziel Dener Damasceno
  2. Catarina A Marques
  3. Dario Beraldi
  4. Kathryn Crouch
  5. Craig Lapsley
  6. Ricardo Obonaga
  7. Luiz R O Tosi
  8. Richard McCulloch
(2020)
Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication
eLife 9:e58030.
https://doi.org/10.7554/eLife.58030
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Abstract

DNA replication is needed to duplicate a cell's genome in S-phase and segregate it during cell division. Previous work in Leishmania detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S-phase. Here, we show that acetylated histone H3 (AcH3), base J and a kinetochore factor colocalise in each chromosome at only a single locus, which corresponds with previously mapped DNA replication initiation regions and is demarcated by localised G/T skew and G4 patterns. In addition, we describe previously undetected subtelomeric DNA replication in G2/M and G1 phase-enriched cells. Finally, we show that subtelomeric DNA replication, unlike chromosome-internal DNA replication, is sensitive to hydroxyurea and dependent on 9-1-1 activity. These findings indicate that Leishmania's genome duplication programme employs subtelomeric DNA replication initiation, possibly extending beyond S-phase, to support predominantly chromosome-internal DNA replication initiation within S-phase.

Data availability

Sequences used in this study have been deposited in the European Nucleotide Archive. Data can be accessed using the accession number PRJEB35027.

The following data sets were generated

Article and author information

Author details

  1. Jeziel Dener Damasceno

    The Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation,, University of Glasgow, Glasgow, United Kingdom
    For correspondence
    jeziel.damasceno@glasgow.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2077-3214

  2. Catarina A Marques

    The Wellcome 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1324-5448

  3. Dario Beraldi

    The Wellcome 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. Kathryn Crouch

    The Wellcome 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9310-4762

  5. 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.

  6. Ricardo Obonaga

    Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
    Competing interests
    The authors declare that no competing interests exist.

  7. Luiz R O Tosi

    Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
    Competing interests
    The authors declare that no competing interests exist.

  8. Richard McCulloch

    The Wellcome 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5739-976X

Funding

Biotechnology and Biological Sciences Research Council (BB/N016165/1)

  • Luiz R O Tosi
  • Richard McCulloch

Biotechnology and Biological Sciences Research Council (BB/R017166/1)

  • Richard McCulloch

European Commission (RECREPEMLE)

  • Jeziel Dener Damasceno

Wellcome (104111)

  • Richard McCulloch

Medical Research Council (MR/S019472/1)

  • Jeziel Dener Damasceno
  • Richard McCulloch

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Christine Clayton, DKFZ-ZMBH Alliance, Germany

Version history

  1. Received: April 17, 2020
  2. Accepted: September 7, 2020
  3. Accepted Manuscript published: September 8, 2020 (version 1)
  4. Version of Record published: September 23, 2020 (version 2)

Copyright

© 2020, Damasceno 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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  1. Jeziel Dener Damasceno
  2. Catarina A Marques
  3. Dario Beraldi
  4. Kathryn Crouch
  5. Craig Lapsley
  6. Ricardo Obonaga
  7. Luiz R O Tosi
  8. Richard McCulloch
(2020)
Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication
eLife 9:e58030.
https://doi.org/10.7554/eLife.58030

Share this article

https://doi.org/10.7554/eLife.58030

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