ArticleNature2009
A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei.
Article in Nature, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
94 citing papers in PubMed, 168 citations in OpenAlex.
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- Next generation genetic screens in kinetoplastids.Nucleic acids research · 2025Review
- Unwrap RAP1's Mystery at Kinetoplastid Telomeres.Biomolecules · 2024Review
- Identifying Antigenic Switching by Clonal Cell Barcoding and Nanopore Sequencing inBio-protocol · 2023Article
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- RAD51-mediated R-loop formation acts to repair transcription-associated DNA breaks driving antigenic variation inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Decoding the impact of nuclear organization on antigenic variation in parasites.Nature microbiology · 2023Review
- Identification of a small-molecule inhibitor that selectively blocks DNA-binding by Trypanosoma brucei replication protein A1.Nature communications · 2023Article
- Competition among variants is predictable and contributes to the antigenic variation dynamics of African trypanosomes.PLoS pathogens · 2023Article
- Telomere maintenance in African trypanosomes.Frontiers in molecular biosciences · 2023Review
- Article
- POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes.Nucleic acids research · 2022Article
- Shared Mechanisms for Mutually Exclusive Expression and Antigenic Variation by Protozoan Parasites.Frontiers in cell and developmental biology · 2022Review
- Article
- DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.PLoS pathogens · 2021Article
- Regulation of Antigenic Variation byPathogens (Basel, Switzerland) · 2021Review
- TbTRF suppresses the TERRA level and regulates the cell cycle-dependent TERRA foci number with a TERRA binding activity in its C-terminal Myb domain.Nucleic acids research · 2021Article
- The MRN complex promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes.Nucleic acids research · 2021Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Trypanosoma brucei is the causative agent of African sleeping sickness in humans and one of the causes of nagana in cattle. This protozoan parasite evades the host immune system by antigenic variation, a periodic switching of its variant surface glycoprotein (VSG) coat. VSG switching is spontaneous and occurs at a rate of about 10(-2)-10(-3) per population doubling in recent isolates from nature, but at a markedly reduced rate (10(-5)-10(-6)) in laboratory-adapted strains. VSG switching is thought to occur predominantly through gene conversion, a form of homologous recombination initiated by a DNA lesion that is used by other pathogens (for example, Candida albicans, Borrelia sp. and Neisseria gonorrhoeae) to generate surface protein diversity, and by B lymphocytes of the vertebrate immune system to generate antibody diversity. Very little is known about the molecular mechanism of VSG switching in T. brucei. Here we demonstrate that the introduction of a DNA double-stranded break (DSB) adjacent to the approximately 70-base-pair (bp) repeats upstream of the transcribed VSG gene increases switching in vitro approximately 250-fold, producing switched clones with a frequency and features similar to those generated early in an infection. We were also able to detect spontaneous DSBs within the 70-bp repeats upstream of the actively transcribed VSG gene, indicating that a DSB is a natural intermediate of VSG gene conversion and that VSG switching is the result of the resolution of this DSB by break-induced replication.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.