ArticlePloS one2016
Trypanosoma brucei TIF2 and TRF Suppress VSG Switching Using Overlapping and Independent Mechanisms.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- TelAP2 links TelAP1 to the telomere complex in Trypanosoma brucei.Scientific reports · 2024Article
- Unwrap RAP1's Mystery at Kinetoplastid Telomeres.Biomolecules · 2024Review
- 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
- Telomere maintenance in African trypanosomes.Frontiers in molecular biosciences · 2023Review
- Proteomic analysis defines the interactome of telomerase in the protozoan parasite,Frontiers in cell and developmental biology · 2023Article
- Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei.Nature microbiology · 2022Article
- 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
- The MRN complex promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes.Nucleic acids research · 2021Article
- Keeping Balance Between Genetic Stability and Plasticity at the Telomere and Subtelomere ofFrontiers in cell and developmental biology · 2021Review
- Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation.Nucleic acids research · 2020Article
- Telomere and Subtelomere R-loops and Antigenic Variation in Trypanosomes.Journal of molecular biology · 2020Review
- Trypanosoma brucei RAP1 Has Essential Functional Domains That Are Required for Different Protein Interactions.mSphere · 2020Article
- 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
- Evaluation of mechanisms that may generate DNA lesions triggering antigenic variation in African trypanosomes.PLoS pathogens · 2018Review
- TelAP1 links telomere complexes with developmental expression site silencing in African trypanosomes.Nucleic acids research · 2018Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Trypanosoma brucei causes debilitating human African trypanosomiasis and evades the host's immune response by regularly switching its major surface antigen, VSG, which is expressed exclusively from subtelomeric loci. We previously showed that two interacting telomere proteins, TbTRF and TbTIF2, are essential for cell proliferation and suppress VSG switching by inhibiting DNA recombination events involving the whole active VSG expression site. We now find that TbTIF2 stabilizes TbTRF protein levels by inhibiting their degradation by the 26S proteasome, indicating that decreased TbTRF protein levels in TbTIF2-depleted cells contribute to more frequent VSG switching and eventual cell growth arrest. Surprisingly, although TbTIF2 depletion leads to more subtelomeric DNA double strand breaks (DSBs) that are both potent VSG switching inducers and detrimental to cell viability, TbTRF depletion does not increase the amount of DSBs inside subtelomeric VSG expression sites. Furthermore, expressing an ectopic allele of F2H-TbTRF in TbTIF2 RNAi cells allowed cells to maintain normal TbTRF protein levels for a longer frame of time. This resulted in a mildly better cell growth and partially suppressed the phenotype of increased VSG switching frequency but did not suppress the phenotype of more subtelomeric DSBs in TbTIF2-depleted cells. Therefore, TbTIF2 depletion has two parallel effects: decreased TbTRF protein levels and increased subtelomeric DSBs, both resulting in an acute increased VSG switching frequency and eventual cell growth arrest.
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