Evidence map›Paper›PMID 20615954›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

Essential roles for imuA'- and imuB-encoded accessory factors in DnaE2-dependent mutagenesis in Mycobacterium tuberculosis.

Digby F Warner, Duduzile E Ndwandwe, Garth L Abrahams, Bavesh D Kana, Edith E Machowski, Ceslovas Venclovas, Valerie Mizrahi

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
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

70 citing papers in PubMed, 129 citations in OpenAlex.

  1. Article
  2. Journal of bacteriology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Expression ofFrontiers in cellular and infection microbiology · 2025
    Article
  8. An additional proofreader contributes to DNA replication fidelity in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. ACS chemical biology · 2022
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

10 more citing papers are in PubMed but not listed here.

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

7 authors at 4 institutions in 2 countries.

Digby F WarnerMedical Research Council/National Health Laboratory Service/University of the Witwatersrand Molecular Mycobacteriology Research Unit and Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Health Sciences, University of the Witwatersrand and the National Health Laboratory Service, Johannesburg 2000, South Africa. digby.warner@nhls.ac.za
Duduzile E Ndwandwe
Garth L Abrahams
Bavesh D Kana
Edith E Machowski
Ceslovas Venclovas
Valerie Mizrahi
University of the Witwatersrand · ZANational Research Foundation · ZANational Health Laboratory Service · ZAVilnius University · LT

Funding

South Africa Tuberculosis AIDS Training (SATBAT)U2RTW007370 · FIC · WITS HEALTH CONSORTIUM (PTY), LTD · PI MARTINSON, NEIL A · 2007 to 2011
$1.9M
FIC NIH HHS U2R TW007370Howard Hughes Medical InstitutePHS HHS 1U2RTW007370/3
6 · The paper itself

Abstract

In Mycobacterium tuberculosis (Mtb), damage-induced mutagenesis is dependent on the C-family DNA polymerase, DnaE2. Included with dnaE2 in the Mtb SOS regulon is a putative operon comprising Rv3395c, which encodes a protein of unknown function restricted primarily to actinomycetes, and Rv3394c, which is predicted to encode a Y-family DNA polymerase. These genes were previously identified as components of an imuA-imuB-dnaE2-type mutagenic cassette widespread among bacterial genomes. Here, we confirm that Rv3395c (designated imuA') and Rv3394c (imuB) are individually essential for induced mutagenesis and damage tolerance. Yeast two-hybrid analyses indicate that ImuB interacts with both ImuA' and DnaE2, as well as with the beta-clamp. Moreover, disruption of the ImuB-beta clamp interaction significantly reduces induced mutagenesis and damage tolerance, phenocopying imuA', imuB, and dnaE2 gene deletion mutants. Despite retaining structural features characteristic of Y-family members, ImuB homologs lack conserved active-site amino acids required for polymerase activity. In contrast, replacement of DnaE2 catalytic residues reproduces the dnaE2 gene deletion phenotype, strongly implying a direct role for the alpha-subunit in mutagenic lesion bypass. These data implicate differential protein interactions in specialist polymerase function and identify the split imuA'-imuB/dnaE2 cassette as a compelling target for compounds designed to limit mutagenesis in a pathogen increasingly associated with drug resistance.

Indexed as

Amino Acid MotifsAmino Acid SequenceBacterial ProteinsBiocatalysisCatalytic DomainDNA DamageDNA-Directed DNA PolymeraseMolecular Sequence DataMutagenesis, InsertionalMycobacterium tuberculosisProtein BindingProtein Structure, SecondaryStructure-Activity RelationshipBacterial ProteinsDNA-Directed DNA Polymerase

Identifiers

PMID20615954
PMCPMC2919956
OpenAlexW2122874344

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.