ArticlePLoS pathogens2010
TOPO3alpha influences antigenic variation by monitoring expression-site-associated VSG switching in Trypanosoma brucei.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 76 citations in OpenAlex.
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- A structural classification of the variant surface glycoproteins of the African trypanosome.PLoS neglected tropical diseases · 2023Article
- A tale of topoisomerases and the knotty genetic material in the backdrop of Plasmodium biology.Bioscience reports · 2022Review
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- POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes.Nucleic acids research · 2022Article
- 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
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression.Frontiers in cell and developmental biology · 2021Review
- Genetic Interaction Between Site-Specific Epigenetic Marks and Roles of H4v in Transcription Termination inFrontiers in cell and developmental biology · 2021Article
- Keeping Balance Between Genetic Stability and Plasticity at the Telomere and Subtelomere ofFrontiers in cell and developmental biology · 2021Review
- DNA Topoisomerase 3α Is Involved in Homologous Recombination Repair and Replication Stress Response inFrontiers in cell and developmental biology · 2021Article
- Read, Write, Adapt: Challenges and Opportunities during Kinetoplastid Genome Replication.Trends in genetics : TIG · 2021Review
- Telomere and Subtelomere R-loops and Antigenic Variation in Trypanosomes.Journal of molecular biology · 2020Review
- Trypanosoma brucei ATR Links DNA Damage Signaling during Antigenic Variation with Regulation of RNA Polymerase I-Transcribed Surface Antigens.Cell reports · 2020Article
- Escaping the immune system by DNA repair and recombination in African trypanosomes.Open biology · 2019Review
- African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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2 authors at 1 institution in 1 country.
Funding
Abstract
Homologous recombination (HR) mediates one of the major mechanisms of trypanosome antigenic variation by placing a different variant surface glycoprotein (VSG) gene under the control of the active expression site (ES). It is believed that the majority of VSG switching events occur by duplicative gene conversion, but only a few DNA repair genes that are central to HR have been assigned a role in this process. Gene conversion events that are associated with crossover are rarely seen in VSG switching, similar to mitotic HR. In other organisms, TOPO3alpha (Top3 in yeasts), a type IA topoisomerase, is part of a complex that is involved in the suppression of crossovers. We therefore asked whether a related mechanism might suppress VSG recombination. Using a set of reliable recombination and switching assays that could score individual switching mechanisms, we discovered that TOPO3alpha function is conserved in Trypanosoma brucei and that TOPO3alpha plays a critical role in antigenic switching. Switching frequency increased 10-40-fold in the absence of TOPO3alpha and this hyper-switching phenotype required RAD51. Moreover, the preference of 70-bp repeats for VSG recombination was mitigated, while homology regions elsewhere in ES were highly favored, in the absence of TOPO3alpha. Our data suggest that TOPO3alpha may remove undesirable recombination intermediates constantly arising between active and silent ESs, thereby balancing ES integrity against VSG recombination.
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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.