ArticleNucleic acids research2014
Suppression of subtelomeric VSG switching by Trypanosoma brucei TRF requires its TTAGGG repeat-binding activity.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- Unwrap RAP1's Mystery at Kinetoplastid Telomeres.Biomolecules · 2024Review
- Identifying Antigenic Switching by Clonal Cell Barcoding and Nanopore Sequencing inBio-protocol · 2023Article
- 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
- UMSBP2 is chromatin remodeler that functions in regulation of gene expression and suppression of antigenic variation in trypanosomes.Nucleic acids research · 2023Article
- Genome-wide subcellular protein map for the flagellate parasite Trypanosoma brucei.Nature microbiology · 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
- In vivo architecture of the telomerase RNA catalytic core in Trypanosoma brucei.Nucleic acids research · 2021Article
- DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.PLoS pathogens · 2021Article
- A nuclear enterprise: zooming in on nuclear organization and gene expression control in the African trypanosome.Parasitology · 2021Review
- Diverse telomeres in trypanosomatids.Parasitology · 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
- TbSAP is a novel chromatin protein repressing metacyclic variant surface glycoprotein expression sites in bloodstream form Trypanosoma brucei.Nucleic acids research · 2021Article
- Keeping Balance Between Genetic Stability and Plasticity at the Telomere and Subtelomere ofFrontiers in cell and developmental biology · 2021Review
- Editorial: Telomere Flexibility and Versatility: A Role of Telomeres in Adaptive Potential.Frontiers in genetics · 2021Article
- Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation.Nucleic acids research · 2020Article
- Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Trypanosoma brucei causes human African trypanosomiasis and regularly switches its major surface antigen, VSG, in the bloodstream of its mammalian host to evade the host immune response. VSGs are expressed exclusively from subtelomeric loci, and we have previously shown that telomere proteins TbTIF2 and TbRAP1 play important roles in VSG switching and VSG silencing regulation, respectively. We now discover that the telomere duplex DNA-binding factor, TbTRF, also plays a critical role in VSG switching regulation, as a transient depletion of TbTRF leads to significantly more VSG switching events. We solved the NMR structure of the DNA-binding Myb domain of TbTRF, which folds into a canonical helix-loop-helix structure that is conserved to the Myb domains of mammalian TRF proteins. The TbTRF Myb domain tolerates well the bulky J base in T. brucei telomere DNA, and the DNA-binding affinity of TbTRF is not affected by the presence of J both in vitro and in vivo. In addition, we find that point mutations in TbTRF Myb that significantly reduced its in vivo telomere DNA-binding affinity also led to significantly increased VSG switching frequencies, indicating that the telomere DNA-binding activity is critical for TbTRF's role in VSG switching regulation.
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Registered trials
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.