DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.

Antigenic variation is an immune evasion strategy used by Trypanosoma brucei that results in the periodic exchange of the surface protein coat. This process is facilitated by the movement of variant surface glycoprotein genes in or out of a specialized locus known as bloodstream form expression site...

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Autores principales:	Alix Thivolle, Ann-Kathrin Mehnert, Eliane Tihon, Emilia McLaughlin, Annick Dujeancourt-Henry, Lucy Glover
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/31e13eb5031649dba360298ff464beb3
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spelling	oai:doaj.org-article:31e13eb5031649dba360298ff464beb32021-12-02T19:59:57ZDNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.1553-73661553-737410.1371/journal.ppat.1010038https://doaj.org/article/31e13eb5031649dba360298ff464beb32021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1010038https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Antigenic variation is an immune evasion strategy used by Trypanosoma brucei that results in the periodic exchange of the surface protein coat. This process is facilitated by the movement of variant surface glycoprotein genes in or out of a specialized locus known as bloodstream form expression site by homologous recombination, facilitated by blocks of repetitive sequence known as the 70-bp repeats, that provide homology for gene conversion events. DNA double strand breaks are potent drivers of antigenic variation, however where these breaks must fall to elicit a switch is not well understood. To understand how the position of a break influences antigenic variation we established a series of cell lines to study the effect of an I-SceI meganuclease break in the active expression site. We found that a DNA break within repetitive regions is not productive for VSG switching, and show that the break position leads to a distinct gene expression profile and DNA repair response which dictates how antigenic variation proceeds in African trypanosomes.Alix ThivolleAnn-Kathrin MehnertEliane TihonEmilia McLaughlinAnnick Dujeancourt-HenryLucy GloverPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 11, p e1010038 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Alix Thivolle Ann-Kathrin Mehnert Eliane Tihon Emilia McLaughlin Annick Dujeancourt-Henry Lucy Glover DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.
description	Antigenic variation is an immune evasion strategy used by Trypanosoma brucei that results in the periodic exchange of the surface protein coat. This process is facilitated by the movement of variant surface glycoprotein genes in or out of a specialized locus known as bloodstream form expression site by homologous recombination, facilitated by blocks of repetitive sequence known as the 70-bp repeats, that provide homology for gene conversion events. DNA double strand breaks are potent drivers of antigenic variation, however where these breaks must fall to elicit a switch is not well understood. To understand how the position of a break influences antigenic variation we established a series of cell lines to study the effect of an I-SceI meganuclease break in the active expression site. We found that a DNA break within repetitive regions is not productive for VSG switching, and show that the break position leads to a distinct gene expression profile and DNA repair response which dictates how antigenic variation proceeds in African trypanosomes.
format	article
author	Alix Thivolle Ann-Kathrin Mehnert Eliane Tihon Emilia McLaughlin Annick Dujeancourt-Henry Lucy Glover
author_facet	Alix Thivolle Ann-Kathrin Mehnert Eliane Tihon Emilia McLaughlin Annick Dujeancourt-Henry Lucy Glover
author_sort	Alix Thivolle
title	DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.
title_short	DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.
title_full	DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.
title_fullStr	DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.
title_full_unstemmed	DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.
title_sort	dna double strand break position leads to distinct gene expression changes and regulates vsg switching pathway choice.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/31e13eb5031649dba360298ff464beb3
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DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.

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