Bacterial ImuABC damage-induced mutagenesis

A reusable bacterial module for SOS-regulated, error-prone DNA synthesis by an ImuA-ImuB-DnaE2 cassette. RecA-dependent DNA-damage signaling and a LexA-family repressor provide a common but regulon-specific induction gate. ImuA and catalytically inactive ImuB organize access of the DnaE2 polymerase to stalled or damaged replication intermediates, where DnaE2 performs damage-tolerant, mutagenic DNA synthesis. Canonical nucleotide excision, homologous recombination, and constitutive chromosome replication are outside the module boundary.

MODULE:bacterial_imuabc_damage_induced_mutagenesisDRAFTBiological Processmodules/bacterial_imuabc_damage_induced_mutagenesis.yaml

translesion synthesisGO:0019985

GO:0019985

translesion synthesis

GO:0019985 provides the defining biological-process boundary; mutagenic output is condition-dependent.

PMID:15458417

Widespread distribution of a lexA-regulated DNA damage-inducible multiple gene cassette in the Proteobacteria phylum.

The study identifies a conserved LexA-regulated, DNA-damage-inducible cassette containing imuA, imuB, and dnaE2-family genes.

PMID:15886391

An SOS-regulated operon involved in damage-inducible mutagenesis in Caulobacter crescentus.

Ortholog deletion genetics establishes all three cassette proteins as a cooperating damage-tolerance and mutagenesis system.

PMID:20615954

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

ImuB binds ImuA, DnaE2, and the beta clamp but lacks polymerase catalytic residues; DnaE2 supplies the polymerase activity.

PMID:17331811

Study of involvement of ImuB and DnaE2 in stationary-phase mutagenesis in Pseudomonas putida.

Species-specific experiments show antagonistic, condition-dependent effects of ImuB and DnaE2 on stationary-phase and UV mutagenesis.

PMID:28118378

DNA Polymerases ImuC and DinB Are Involved in DNA Alkylation Damage Tolerance in Pseudomonas aeruginosa and Pseudomonas putida.

P. putida ImuC/DnaE2 contributes to tolerance of methylating DNA damage.

PMID:37625357

DinB (DNA polymerase IV), ImuBC and RpoS contribute to the generation of ciprofloxacin-resistance mutations in Pseudomonas aeruginosa.

P. aeruginosa experiments provide close-relative evidence that ImuBC contributes to antibiotic-resistance mutation generation.

file:projects/P_PUTIDA/data/psepk_gene_list.tsv

PSEPK UniProt metadata table

PP_3116 through PP_3119 provide exact KT2440 exemplars for LexA2, ImuA, ImuB, and DnaE2; Q88ME4 provides the RecA signal exemplar.

The three-part ImuA-ImuB-DnaE2 effector is the reusable core. RecA and LexA regulation are represented as optional upstream parts because cassette control and LexA paralog assignment vary among bacteria. In KT2440 the local cassette repressor is LexA2 rather than the principal LexA1 SOS repressor.

6Nodes

5Parts

0Variant Sets

0Variants

5Annotons

4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

bacterial_imuabc_damage_induced_mutagenesis-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (5/5 grounded genes reviewed)

4 complete review(s) · 4 with deep research · 0 missing review · 1 reviewed but lacking deep research

Gene	Review	Complete	Deep research
dnaE2 Q88I82	✓	10/11	✓
imuB Q88I83	✓	✓	✓
lexA2 P59479	✓	✓	✓
PP_3117 Q88I84	✓	✓	✗
recA Q88ME4	✓	✓	✓

Tree

bacterial ImuABC damage-induced mutagenesisBiological Processbacterial_imuabc_damage_induced_mutagenesis

Parts
1. 1. RecA-dependent DNA-damage signaling optional
2. activated RecA damage signalBiological Processreca_damage_signal
  
  Annotons
  - RecA nucleoprotein damage sensor Family: bacterial RecA family
3. 2. LexA-family repression and damage-induced derepression optional
4. LexA cassette regulatory gateBiological Processlexa_cassette_gate
  
  Annotons
  - cassette-specific LexA repressor Family: LexA repressor family
5. 3. ImuA translesion-synthesis accessory function
6. ImuA accessory stepBiological Processimua_accessory
  
  Annotons
  - ImuA translesion-synthesis accessory protein Family: ImuA family
7. 4. ImuB polymerase-recruitment scaffold
8. ImuB recruitment stepBiological Processimub_recruitment
  
  Annotons
  - ImuB translesion-synthesis accessory protein Family: ImuB/IMS family
9. 5. DnaE2-dependent mutagenic DNA synthesis
10. DnaE2 error-prone DNA synthesisBiological Processdnae2_mutagenic_synthesis
  
  Annotons
  - DnaE2 error-prone DNA polymerase Family: DnaE2 family

Details

Context

bacteriaNCBITaxon:2

bacterial ImuABC damage-induced mutagenesisBiological Processbacterial_imuabc_damage_induced_mutagenesis

translesion synthesisGO:0019985

Context

bacteriaNCBITaxon:2

Connections

reca_damage_signal -> lexa_cassette_gate Positively Regulates

Activated RecA promotes LexA-family autocleavage; application to KT2440 LexA2 is a family-level inference rather than a direct cleavage result.

lexa_cassette_gate -> imua_accessory Negatively Regulates

Intact cassette-associated LexA represses transcription of the ImuABC effector genes.

imua_accessory -> imub_recruitment Provides Input For

ImuA engages the ImuB-centered adaptor before DnaE2 recruitment.

imub_recruitment -> dnae2_mutagenic_synthesis Provides Input For

ImuB recruits or organizes DnaE2 at the damaged replication intermediate.

Part 1: RecA-dependent DNA-damage signaling (optional)

activated RecA damage signalBiological Processreca_damage_signal

Annotons

RecA nucleoprotein damage sensor

reca_damage_sensor

Participant: Family: bacterial RecA family

Family:

bacterial RecA familyPANTHER:PTHR45900

Representative Members: PSEPK RecAUniProtKB:Q88ME4

Required Function:

ATP-dependent DNA damage sensor activityGO:0140664

Function

ATP-dependent DNA damage sensor activityGO:0140664

Processes

SOS responseGO:0009432

Couples damage-generated single-stranded DNA to LexA-family repressor autocleavage.

Part 2: LexA-family repression and damage-induced derepression (optional)

LexA cassette regulatory gateBiological Processlexa_cassette_gate

Annotons

cassette-specific LexA repressor

lexa_cassette_repressor

Participant: Family: LexA repressor family

Family:

LexA repressor familyPANTHER:PTHR33516

Representative Members: PSEPK LexA2UniProtKB:P59479

Required Function:

DNA-binding transcription repressor activityGO:0001217

Function

DNA-binding transcription repressor activityGO:0001217

Processes

negative regulation of DNA-templated transcriptionGO:0045892

Represses cassette transcription until the DNA-damage signal triggers LexA-family autocleavage and derepression.

Part 3: ImuA translesion-synthesis accessory function

ImuA accessory stepBiological Processimua_accessory

Annotons

ImuA translesion-synthesis accessory protein

imua_accessory_protein

Participant: Family: ImuA family

Family:

ImuA familyInterPro:IPR047610

Representative Members: PSEPK ImuAUniProtKB:Q88I84

Processes

translesion synthesisGO:0019985

Accessory cassette component required for effective DnaE2-dependent damage-induced synthesis.

file:PSEPK/PP_3117/PP_3117-uniprot.txt

Q88I84 carries the ImuA-specific IPR047610 and PTHR35369:SF3 assignments.

Part 4: ImuB polymerase-recruitment scaffold

ImuB recruitment stepBiological Processimub_recruitment

Annotons

ImuB translesion-synthesis accessory protein

imub_accessory_protein

Participant: Family: ImuB/IMS family

Family:

ImuB/IMS familyPfam:PF00817

Representative Members: PSEPK ImuBUniProtKB:Q88I83

Function

protein-macromolecule adaptor activityGO:0030674

Processes

translesion synthesisGO:0019985

Catalytically inactive polymerase-like adaptor that recruits DnaE2 and replication-clamp machinery to damaged DNA.

file:PSEPK/imuB/imuB-uniprot.txt

Q88I83 carries the IMS/PF00817 and UmuC-fold assignments but is not annotated as the cassette polymerase.

PMID:20615954

Ortholog ImuB binds ImuA, DnaE2, and the beta clamp and lacks polymerase active-site residues.

Part 5: DnaE2-dependent mutagenic DNA synthesis

DnaE2 error-prone DNA synthesisBiological Processdnae2_mutagenic_synthesis

Annotons

DnaE2 error-prone DNA polymerase

dnae2_polymerase

Participant: Family: DnaE2 family

Family:

DnaE2 familyInterPro:IPR023073

Representative Members: PSEPK DnaE2UniProtKB:Q88I82

Required Function:

DNA-directed DNA polymerase activityGO:0003887

Function

DNA-directed DNA polymerase activityGO:0003887

Substrates: damaged or lesion-containing DNA primer-template deoxyribonucleoside triphosphates

Products: extended DNA containing damage-bypass synthesis

Processes

translesion synthesisGO:0019985

Performs damage-tolerant DNA synthesis after ImuA/ImuB-dependent recruitment; mutational output is context dependent.