ArticlePLoS genetics2020
Conditional knockout of RAD51-related genes in Leishmania major reveals a critical role for homologous recombination during genome replication.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Towards precision antileishmanial drug discovery: Integrating multi-omics, functional genomics, artificial intelligence and host-directed therapeutics.Molecular biology reports · 2026Review
- 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
- A comprehensive review of CRISPR-Cas9-mediated genome editing in Leishmania strains: methodologies, applications, challenges and future directions.Molecular biology reports · 2026Review
- The nuclear basket nucleoporin MLP1 is required to maintain nuclear integrity, and mitotic fidelity in Trypanosoma brucei.PLoS neglected tropical diseases · 2026Article
- High-Throughput Cell Cycle and Morphological Analysis of Leishmania mexicana and Other Kinetoplastids.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Genetic Manipulation Tools in Leishmania: From CRISPR/Cas9 to Vaccine Strategies for Disease Control.Acta parasitologica · 2025Review
- ATR, a DNA damage kinase, modulates DNA replication timing in Leishmania major.PLoS genetics · 2025Article
- Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms.BMC genomics · 2025Article
- Translesion synthesis and microhomology-mediated end-joining repair in trypanosomatids.PLoS neglected tropical diseases · 2025Review
- Leishmania major chromosomes are replicated from a single high-efficiency locus supplemented by thousands of lower efficiency initiation events.Cell reports · 2025Article
- Article
- R-loops acted on by RNase H1 influence DNA replication timing and genome stability in Leishmania.Nature communications · 2025Article
- Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei.Nature communications · 2025Article
- Recent advances in the genetic engineering of theIranian journal of basic medical sciences · 2025Review
- Recent Advances in CRISPR/Cas9-Mediated Genome Editing in Leishmania Strains.Acta parasitologica · 2024Review
- Established and emerging techniques for the study of microglia: visualization, depletion, and fate mapping.Frontiers in cellular neuroscience · 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
- Immunoprecipitation of RNA-DNA hybrid interacting proteins in Trypanosoma brucei reveals conserved and novel activities, including in the control of surface antigen expression needed for immune evasion by antigenic variation.Nucleic acids research · 2023Article
- CRISPR-Cas Technology as a Revolutionary Genome Editing tool: Mechanisms and Biomedical Applications.Iranian biomedical journal · 2023Review
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Homologous recombination (HR) has an intimate relationship with genome replication, both during repair of DNA lesions that might prevent DNA synthesis and in tackling stalls to the replication fork. Recent studies led us to ask if HR might have a more central role in replicating the genome of Leishmania, a eukaryotic parasite. Conflicting evidence has emerged regarding whether or not HR genes are essential, and genome-wide mapping has provided evidence for an unorthodox organisation of DNA replication initiation sites, termed origins. To answer this question, we have employed a combined CRISPR/Cas9 and DiCre approach to rapidly generate and assess the effect of conditional ablation of RAD51 and three RAD51-related proteins in Leishmania major. Using this approach, we demonstrate that loss of any of these HR factors is not immediately lethal but in each case growth slows with time and leads to DNA damage and accumulation of cells with aberrant DNA content. Despite these similarities, we show that only loss of RAD51 or RAD51-3 impairs DNA synthesis and causes elevated levels of genome-wide mutation. Furthermore, we show that these two HR factors act in distinct ways, since ablation of RAD51, but not RAD51-3, has a profound effect on DNA replication, causing loss of initiation at the major origins and increased DNA synthesis at subtelomeres. Our work clarifies questions regarding the importance of HR to survival of Leishmania and reveals an unanticipated, central role for RAD51 in the programme of genome replication in a microbial eukaryote.
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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.