Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.

Trypanosoma brucei is a master of antigenic variation and immune response evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface Glycoprotein-encoding genes (VSGs), T. brucei can change its protein coat by "switching" from the expression of one VSG to another. Each activ...

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Autores principales:	Galadriel A Hovel-Miner, Catharine E Boothroyd, Monica Mugnier, Oliver Dreesen, George A M Cross, F Nina Papavasiliou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2ac56ca86ee74f68815bab01b552c435
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spelling	oai:doaj.org-article:2ac56ca86ee74f68815bab01b552c4352021-11-18T06:04:00ZTelomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.1553-73661553-737410.1371/journal.ppat.1002900https://doaj.org/article/2ac56ca86ee74f68815bab01b552c4352012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22952449/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Trypanosoma brucei is a master of antigenic variation and immune response evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface Glycoprotein-encoding genes (VSGs), T. brucei can change its protein coat by "switching" from the expression of one VSG to another. Each active VSG is monoallelically expressed from only one of approximately 15 subtelomeric sites. Switching VSG expression occurs by three predominant mechanisms, arguably the most significant of which is the non-reciprocal exchange of VSG containing DNA by duplicative gene conversion (GC). How T. brucei orchestrates its complex switching mechanisms remains to be elucidated. Recent work has demonstrated that an exogenous DNA break in the active site could initiate a GC based switch, yet the source of the switch-initiating DNA lesion under natural conditions is still unknown. Here we investigated the hypothesis that telomere length directly affects VSG switching. We demonstrate that telomerase deficient strains with short telomeres switch more frequently than genetically identical strains with long telomeres and that, when the telomere is short, switching preferentially occurs by GC. Our data supports the hypothesis that a short telomere at the active VSG expression site results in an increase in subtelomeric DNA breaks, which can initiate GC based switching. In addition to their significance for T. brucei and telomere biology, the findings presented here have implications for the many diverse pathogens that organize their antigenic genes in subtelomeric regions.Galadriel A Hovel-MinerCatharine E BoothroydMonica MugnierOliver DreesenGeorge A M CrossF Nina PapavasiliouPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 8, p e1002900 (2012)
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 Galadriel A Hovel-Miner Catharine E Boothroyd Monica Mugnier Oliver Dreesen George A M Cross F Nina Papavasiliou Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.
description	Trypanosoma brucei is a master of antigenic variation and immune response evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface Glycoprotein-encoding genes (VSGs), T. brucei can change its protein coat by "switching" from the expression of one VSG to another. Each active VSG is monoallelically expressed from only one of approximately 15 subtelomeric sites. Switching VSG expression occurs by three predominant mechanisms, arguably the most significant of which is the non-reciprocal exchange of VSG containing DNA by duplicative gene conversion (GC). How T. brucei orchestrates its complex switching mechanisms remains to be elucidated. Recent work has demonstrated that an exogenous DNA break in the active site could initiate a GC based switch, yet the source of the switch-initiating DNA lesion under natural conditions is still unknown. Here we investigated the hypothesis that telomere length directly affects VSG switching. We demonstrate that telomerase deficient strains with short telomeres switch more frequently than genetically identical strains with long telomeres and that, when the telomere is short, switching preferentially occurs by GC. Our data supports the hypothesis that a short telomere at the active VSG expression site results in an increase in subtelomeric DNA breaks, which can initiate GC based switching. In addition to their significance for T. brucei and telomere biology, the findings presented here have implications for the many diverse pathogens that organize their antigenic genes in subtelomeric regions.
format	article
author	Galadriel A Hovel-Miner Catharine E Boothroyd Monica Mugnier Oliver Dreesen George A M Cross F Nina Papavasiliou
author_facet	Galadriel A Hovel-Miner Catharine E Boothroyd Monica Mugnier Oliver Dreesen George A M Cross F Nina Papavasiliou
author_sort	Galadriel A Hovel-Miner
title	Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.
title_short	Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.
title_full	Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.
title_fullStr	Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.
title_full_unstemmed	Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.
title_sort	telomere length affects the frequency and mechanism of antigenic variation in trypanosoma brucei.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2ac56ca86ee74f68815bab01b552c435
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Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei.

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