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Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination
Antigenic variation in Trypanosoma brucei has selected for the evolution of a massive archive of silent Variant Surface Glycoprotein (VSG) genes, which are activated by recombination into specialized expression sites. Such VSG switching can occur at rates substantially higher than background mutatio...
Autores principales: | , |
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Formato: | Texto |
Lenguaje: | English |
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Blackwell Publishing Ltd
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408642/ https://www.ncbi.nlm.nih.gov/pubmed/18430140 http://dx.doi.org/10.1111/j.1365-2958.2008.06230.x |
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author | Hartley, Claire L McCulloch, Richard |
author_facet | Hartley, Claire L McCulloch, Richard |
author_sort | Hartley, Claire L |
collection | PubMed |
description | Antigenic variation in Trypanosoma brucei has selected for the evolution of a massive archive of silent Variant Surface Glycoprotein (VSG) genes, which are activated by recombination into specialized expression sites. Such VSG switching can occur at rates substantially higher than background mutation and is dependent on homologous recombination, a core DNA repair reaction. A key regulator of homologous recombination is BRCA2, a protein that binds RAD51, the enzyme responsible for DNA strand exchange. Here, we show that T. brucei BRCA2 has undergone a recent, striking expansion in the number of BRC repeats, a sequence element that mediates interaction with RAD51. T. brucei BRCA2 mutants are shown to be significantly impaired in antigenic variation and display genome instability. By generating BRCA2 variants with reduced BRC repeat numbers, we show that the BRC expansion is crucial in determining the efficiency of T. brucei homologous recombination and RAD51 localization. Remarkably, however, this appears not to be a major determinant of the activation of at least some VSG genes. |
format | Text |
id | pubmed-2408642 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-24086422008-06-09 Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination Hartley, Claire L McCulloch, Richard Mol Microbiol Research Articles Antigenic variation in Trypanosoma brucei has selected for the evolution of a massive archive of silent Variant Surface Glycoprotein (VSG) genes, which are activated by recombination into specialized expression sites. Such VSG switching can occur at rates substantially higher than background mutation and is dependent on homologous recombination, a core DNA repair reaction. A key regulator of homologous recombination is BRCA2, a protein that binds RAD51, the enzyme responsible for DNA strand exchange. Here, we show that T. brucei BRCA2 has undergone a recent, striking expansion in the number of BRC repeats, a sequence element that mediates interaction with RAD51. T. brucei BRCA2 mutants are shown to be significantly impaired in antigenic variation and display genome instability. By generating BRCA2 variants with reduced BRC repeat numbers, we show that the BRC expansion is crucial in determining the efficiency of T. brucei homologous recombination and RAD51 localization. Remarkably, however, this appears not to be a major determinant of the activation of at least some VSG genes. Blackwell Publishing Ltd 2008-06 /pmc/articles/PMC2408642/ /pubmed/18430140 http://dx.doi.org/10.1111/j.1365-2958.2008.06230.x Text en © 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd https://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Research Articles Hartley, Claire L McCulloch, Richard Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination |
title | Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination |
title_full | Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination |
title_fullStr | Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination |
title_full_unstemmed | Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination |
title_short | Trypanosoma brucei BRCA2 acts in antigenic variation and has undergone a recent expansion in BRC repeat number that is important during homologous recombination |
title_sort | trypanosoma brucei brca2 acts in antigenic variation and has undergone a recent expansion in brc repeat number that is important during homologous recombination |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408642/ https://www.ncbi.nlm.nih.gov/pubmed/18430140 http://dx.doi.org/10.1111/j.1365-2958.2008.06230.x |
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