ArticleMolecular microbiology2013
Trypanosoma brucei Orc1 is essential for nuclear DNA replication and affects both VSG silencing and VSG switching.
Article in Molecular microbiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 72 citations in OpenAlex.
- Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei.Nature communications · 2025Article
- An independently tunable dual control system for RNAi complementation in Trypanosoma brucei.PloS one · 2025Article
- Article
- 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
- 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
- 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
- Regulation of Antigenic Variation byPathogens (Basel, Switzerland) · 2021Review
- The CRK2-CYC13 complex functions as an S-phase cyclin-dependent kinase to promote DNA replication in Trypanosoma brucei.BMC biology · 2021Article
- Read, Write, Adapt: Challenges and Opportunities during Kinetoplastid Genome Replication.Trends in genetics : TIG · 2021Review
- 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
- Replication origin location might contribute to genetic variability in Trypanosoma cruzi.BMC genomics · 2020Article
- DNA replication protein Cdc45 directly interacts with PCNA via its PIP box in Leishmania donovani and the Cdc45 PIP box is essential for cell survival.PLoS pathogens · 2020Article
- Identification of a novel base J binding protein complex involved in RNA polymerase II transcription termination in trypanosomes.PLoS genetics · 2020Article
- Trypanosoma brucei ATR Links DNA Damage Signaling during Antigenic Variation with Regulation of RNA Polymerase I-Transcribed Surface Antigens.Cell reports · 2020Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Binding of the Origin Recognition Complex (ORC) to replication origins is essential for initiation of DNA replication, but ORC has non-essential functions outside of DNA replication, including in heterochromatic gene silencing and telomere maintenance. Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis, uses antigenic variation as a major virulence mechanism to evade the host's immune attack by expressing its major surface antigen, the Variant Surface Glycoprotein (VSG), in a monoallelic manner. An Orc1/Cdc6 homologue has been identified in T. brucei, but its role in DNA replication has not been directly confirmed and its potential involvement in VSG repression or switching has not been thoroughly investigated. In this study, we show that TbOrc1 is essential for nuclear DNA replication in mammalian-infectious bloodstream and tsetse procyclic forms (BF and PF). Depletion of TbOrc1 resulted in derepression of telomere-linked silent VSGs in both BF and PF, and increased VSG switching particularly through the in situ transcriptional switching mechanism. TbOrc1 associates with telomere repeats but appears to do so independently of two known T. brucei telomere proteins, TbRAP1 and TbTRF. We conclude that TbOrc1 has conserved functions in DNA replication and is also required to control telomere-linked VSG expression and VSG switching.
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