Evidence map›Paper›PMID 30380080›Full record

ArticleNucleic acids research2018

Conditional genome engineering reveals canonical and divergent roles for the Hus1 component of the 9-1-1 complex in the maintenance of the plastic genome of Leishmania.

Jeziel D Damasceno, Ricardo Obonaga, Gabriel L A Silva, João L Reis-Cunha, Samuel M Duncan, Daniella C Bartholomeu, Jeremy C Mottram, Richard McCulloch, Luiz R O Tosi

Abstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Article
  3. The 9-1-1 complex protects ssDNA gaps in BRCA2-deficient cancer.bioRxiv : the preprint server for biology · 2025
    Article
  4. Article
  5. Life in plastic, it's fantastic! HowFrontiers in cellular and infection microbiology · 2023
    Review
  6. Microevolution ofeLife · 2022
    Article
  7. Impact of Genetic Diversity and Genome Plasticity ofFrontiers in cellular and infection microbiology · 2022
    Review
  8. Review
  9. Unpicking the Roles of DNA Damage Protein Kinases in Trypanosomatids.Frontiers in cell and developmental biology · 2021
    Review
  10. Specific Human ATR and ATM Inhibitors Modulate Single Strand DNA Formation inFrontiers in cellular and infection microbiology · 2021
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Next-Generation Analysis of Trypanosomatid Genome Stability and Instability.Methods in molecular biology (Clifton, N.J.) · 2020
    Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jeziel D DamascenoDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Ricardo ObonagaDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Gabriel L A SilvaDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
João L Reis-CunhaLaboratório de Genômica de Parasitos, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brasil.
Samuel M DuncanWellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.
Daniella C BartholomeuLaboratório de Genômica de Parasitos, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brasil.
Jeremy C MottramWellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.
Richard McCullochWellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.
Luiz R O TosiDepartment of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.

Funding

Medical Research Council G0401553Medical Research Council MR/K019384/1Medical Research Council MR/K019384/2Wellcome TrustWellcome Trust 104111Wellcome Trust 200807/Z/16/Z
6 · The paper itself

Abstract

Leishmania species are protozoan parasites whose remarkably plastic genome limits the establishment of effective genetic manipulation and leishmaniasis treatment. The strategies used by Leishmania to maintain its genome while allowing variability are not fully understood. Here, we used DiCre-mediated conditional gene deletion to show that HUS1, a component of the 9-1-1 (RAD9-RAD1-HUS1) complex, is essential and is required for a G2/M checkpoint. By analyzing genome-wide instability in HUS1 ablated cells, HUS1 is shown to have a conserved role, by which it preserves genome stability and also a divergent role, by which it promotes genome variability. These roles of HUS1 are related to distinct patterns of formation and resolution of single-stranded DNA and γH2A, throughout the cell cycle. Our findings suggest that Leishmania 9-1-1 subunits have evolved to co-opt canonical genomic maintenance and genomic variation functions. Hence, this study reveals a pivotal function of HUS1 in balancing genome stability and transmission in Leishmania. These findings may be relevant to understanding the evolution of genome maintenance and plasticity in other pathogens and eukaryotes.

Indexed as

Genome, ProtozoanCell Cycle ProteinsComputational BiologyCulture MediaDNA Repair EnzymesDNA, Single-StrandedEndonucleasesG2 Phase Cell Cycle CheckpointsGene DeletionGene Expression RegulationGenetic EngineeringGenetic VariationGenomic InstabilityHistonesLeishmania majorWhole Genome SequencingCell Cycle ProteinsCulture MediaDNA Repair EnzymesDNA, Single-StrandedEndonucleasesHistonesrad9 protein

Identifiers

PMID30380080
PMCPMC6294564

What OpenQuestion holds

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Registered trials

None linked

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.