ArticlePLoS pathogens2017
Genome-wide and protein kinase-focused RNAi screens reveal conserved and novel damage response pathways in Trypanosoma brucei.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Genome-wide mapping of replication stress response factors reveals the management of polycistronic transcription, replication initiation, and responses to replication stress in Leishmania.Nucleic acids research · 2026Article
- CRISPR-Cas13b mediated gene knockdowns in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2025Article
- Discovery of unique mitotic mechanisms inOpen biology · 2025Article
- Genome-Wide Libraries for Protozoan Pathogen Drug Target Screening Using Yeast Surface Display.ACS infectious diseases · 2023Article
- Targeting trypanosomes: how chemogenomics and artificial intelligence can guide drug discovery.Biochemical Society transactions · 2023Review
- Article
- Distinguishing functions of trypanosomatid protein kinases.Trends in parasitology · 2022Review
- Structure, function and druggability of the African trypanosome flagellum.Journal of cellular physiology · 2022Review
- Differences in Transporters Rather than Drug Targets Are the Principal Determinants of the Different Innate Sensitivities ofInternational journal of molecular sciences · 2022Article
- Establishment of quantitative RNAi-based forward genetics in Entamoeba histolytica and identification of genes required for growth.PLoS pathogens · 2021Article
- DNA double strand break position leads to distinct gene expression changes and regulates VSG switching pathway choice.PLoS pathogens · 2021Article
- Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host.PLoS neglected tropical diseases · 2021Article
- Arginine Methyltransferases as Regulators of RNA-Binding Protein Activities in Pathogenic Kinetoplastids.Frontiers in molecular biosciences · 2021Review
- Unpicking the Roles of DNA Damage Protein Kinases in Trypanosomatids.Frontiers in cell and developmental biology · 2021Review
- DNA Double-Strand Breaks: A Double-Edged Sword for Trypanosomatids.Frontiers in cell and developmental biology · 2021Review
- Phosphoglycerate kinase: structural aspects and functions, with special emphasis on the enzyme from Kinetoplastea.Open biology · 2020Review
- Polo-like kinase in trypanosomes: an odd member out of the Polo family.Open biology · 2020Article
- Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation.Nucleic acids research · 2020Article
- Conditional knockout of RAD51-related genes in Leishmania major reveals a critical role for homologous recombination during genome replication.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
11 authors.
Funding
Abstract
All cells are subject to structural damage that must be addressed for continued growth. A wide range of damage affects the genome, meaning multiple pathways have evolved to repair or bypass the resulting DNA lesions. Though many repair pathways are conserved, their presence or function can reflect the life style of individual organisms. To identify genome maintenance pathways in a divergent eukaryote and important parasite, Trypanosoma brucei, we performed RNAi screens to identify genes important for survival following exposure to the alkylating agent methyl methanesulphonate. Amongst a cohort of broadly conserved and, therefore, early evolved repair pathways, we reveal multiple activities not so far examined functionally in T. brucei, including DNA polymerases, DNA helicases and chromatin factors. In addition, the screens reveal Trypanosoma- or kinetoplastid-specific repair-associated activities. We also provide focused analyses of repair-associated protein kinases and show that loss of at least nine, and potentially as many as 30 protein kinases, including a nuclear aurora kinase, sensitises T. brucei to alkylation damage. Our results demonstrate the potential for synthetic lethal genome-wide screening of gene function in T. brucei and provide an evolutionary perspective on the repair pathways that underpin effective responses to damage, with particular relevance for related kinetoplastid pathogens. By revealing that a large number of diverse T. brucei protein kinases act in the response to damage, we expand the range of eukaryotic signalling factors implicated in genome maintenance activities.
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