Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation
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...
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doaj-5ec0afd54d284df0a7996f62bb86b7b72021-05-05T00:24:58ZengeLife Sciences Publications LtdeLife2050-084X2016-05-01510.7554/eLife.12765Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variationRebecca Devlin0Catarina A Marques1https://orcid.org/0000-0003-1324-5448Daniel Paape2Marko Prorocic3Andrea C Zurita-Leal4Samantha J Campbell5Craig Lapsley6Nicholas Dickens7Richard McCulloch8https://orcid.org/0000-0001-5739-976XThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomThe Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomSurvival 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.https://elifesciences.org/articles/12765Trypanosomaantigenic variationVariant Surface GlycoproteinDNA repairDNA replicationDNA break |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rebecca Devlin Catarina A Marques Daniel Paape Marko Prorocic Andrea C Zurita-Leal Samantha J Campbell Craig Lapsley Nicholas Dickens Richard McCulloch |
spellingShingle |
Rebecca Devlin Catarina A Marques Daniel Paape Marko Prorocic Andrea C Zurita-Leal Samantha J Campbell Craig Lapsley Nicholas Dickens Richard McCulloch Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation eLife Trypanosoma antigenic variation Variant Surface Glycoprotein DNA repair DNA replication DNA break |
author_facet |
Rebecca Devlin Catarina A Marques Daniel Paape Marko Prorocic Andrea C Zurita-Leal Samantha J Campbell Craig Lapsley Nicholas Dickens Richard McCulloch |
author_sort |
Rebecca Devlin |
title |
Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation |
title_short |
Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation |
title_full |
Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation |
title_fullStr |
Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation |
title_full_unstemmed |
Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation |
title_sort |
mapping replication dynamics in trypanosoma brucei reveals a link with telomere transcription and antigenic variation |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2016-05-01 |
description |
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. |
topic |
Trypanosoma antigenic variation Variant Surface Glycoprotein DNA repair DNA replication DNA break |
url |
https://elifesciences.org/articles/12765 |
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