Bacterial ImuABC damage-induced mutagenesis

A bacterial ImuA-type accessory protein, ImuB adaptor and DnaE2/ImuC polymerase cooperate in damage-tolerant DNA synthesis. This family-grounded realization spans experimentally characterized bacterial lineages without asserting that every bacterium carries the cassette. ImuB couples the accessory protein and polymerase to the replication clamp; DnaE2 supplies DNA synthesis. RecA signaling and LexA-family repression are optional, regulon-specific induction context. Mutational output depends on the organism, damage and growth state: induced mutagenesis and stationary-phase antimutator effects need not conflict. Nucleotide excision repair, homologous recombination and bulk chromosome replication are outside the module boundary, although translesion synthesis itself participates in the broader GO process DNA replication.

MODULE:bacterial_imuabc_damage_induced_mutagenesisCOMPLETECONCRETEBiological Processmodules/bacterial_imuabc_damage_induced_mutagenesis.yaml
translesion synthesisGO:0019985
GO:0019985
translesion synthesis
GO:0019985 provides the defining biological-process boundary. The parent term rather than its mutagenic child GO:0042276 is used module-wide because the mutational output is condition-dependent in at least one exemplar; see notes.
The replication of damaged DNA by synthesis across a lesion in the template strand; a specialized DNA polymerase or replication complex inserts a defined nucleotide across from the lesion which allows DNA synthesis to continue beyond the lesion.
PMID:15458417
Widespread distribution of a lexA-regulated DNA damage-inducible multiple gene cassette in the Proteobacteria phylum.
The cassette is a conserved, LexA-regulated, DNA-damage-inducible unit found across many Proteobacteria families, with its own encoded LexA as the local repressor.
these genes constitute a DNA damage-inducible operon that is regulated by its own encoded LexA protein
PMID:15886391
An SOS-regulated operon involved in damage-inducible mutagenesis in Caulobacter crescentus.
Deletion genetics in Caulobacter crescentus establish all three cassette proteins as one cooperating damage-tolerance and mutagenesis system, induced by damage in a recA-dependent manner.
The results show that the dnaE2 operon is upregulated in response to DNA damage in a recA-dependent manner, and demonstrate that all three genes that compose this expression unit are involved in UV and mitomycin C-induced mutagenesis.
PMID:15886391
An SOS-regulated operon involved in damage-inducible mutagenesis in Caulobacter crescentus.
In the genomes examined in this 2005 study, imuB and dnaE2 co-occurred despite variable operon organization. This historical survey supports coupling, not a universal present-day genome rule or demonstrated activity from co-occurrence alone.
It is very interesting to note that, independently of being organized as single transcriptional units or as independent genes, imuB and dnaE2 always co-exist in bacterial genomes, strongly suggesting that their activities are interconnected.
PMID:20615954
Essential roles for imuA'- and imuB-encoded accessory factors in DnaE2-dependent mutagenesis in Mycobacterium tuberculosis.
M. tuberculosis deletion genetics and interactions of its proteins, together with M. smegmatis functional dissection, establish an accessory-dependent DnaE2 system. The individual deletion, catalytic-site and clamp-function experiments must retain their assay-organism attribution.
Here, we confirm that Rv3395c (designated imuA ′) and Rv3394c ( imuB ) are individually essential for induced mutagenesis and damage tolerance.
PMID:20615954
Essential roles for imuA'- and imuB-encoded accessory factors in DnaE2-dependent mutagenesis in Mycobacterium tuberculosis.
The ImuA-type accessory/ImuB/DnaE2 system is a mechanistically distinct alternative to UmuDC-mediated translesion synthesis. The functional replacement description alone does not establish mutual genomic exclusion; coexistence or absence requires genome-specific evidence.
Therefore, although broadly consistent with the identification of the imuA ′- imuB-dnaE2 cassette as the nonorthologous replacement of the umuDC system ( 5 ), our data reveal a “mutasome” comprising distinct components
PMID:17331811
Study of involvement of ImuB and DnaE2 in stationary-phase mutagenesis in Pseudomonas putida.
Pseudomonas putida is the documented exception to uniformly mutagenic output: ImuB and DnaE2 have antagonistic effects, and DnaE2 suppresses stationary-phase base substitutions.
it acted as an anti-mutator in accumulation of base substitution
PMID:28118378
DNA Polymerases ImuC and DinB Are Involved in DNA Alkylation Damage Tolerance in Pseudomonas aeruginosa and Pseudomonas putida.
Pseudomonas ImuC/DnaE2 contributes to alkylation-damage tolerance and induced mutagenesis. These outcomes differ from the stationary-phase base-substitution assay and prevent interpreting its antimutator result as a universal absence of mutagenic function.
polymerases ImuC and DinB ensured a protective role against N- and O-methylation
PMID:37625357
DinB (DNA polymerase IV), ImuBC and RpoS contribute to the generation of ciprofloxacin-resistance mutations in Pseudomonas aeruginosa.
In Pseudomonas aeruginosa the cassette contributes to the generation of antibiotic-resistance mutations, the clinically relevant output of the module.
are also involved in generating CipR mutations in this organism, since the yields of CipR mutations were substantially decreased in imuB- or imuC-defective cells compared to wild-type
PMID:12705867
DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis.
In M. tuberculosis the DnaE2-dependent output drives survival after damage, virulence and the emergence of drug resistance in vivo.
and can contribute directly to the emergence of drug resistance in vivo
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.
PP_3119
PMID:21475246
Breaking the rules: bacteria that use several DNA polymerase IIIs.
Narrative review distinguishing bacterial C-family replicases from the damage-induced ImuC system. Polymerase fold does not identify which replication role a member performs.
Yet another group of bacteria encode a second Pol III (ImuC)
PMID:36288458
Sending out an SOS - the bacterial DNA damage response.
Comparative SOS review documents lineage-specific regulons and alternative TLS systems, supporting optional RecA/LexA context and taxon-specific cassette assessment.
PMID:38591662
Myxococcus xanthus translesion DNA synthesis protein ImuA is an ATPase enhanced by DNA.
Purified Myxococcus ImuA has DNA-enhanced ATPase activity and DNA binding. These tested activities invalidate a universal no-activity statement, but do not establish the same activities in the existing Caulobacter, Pseudomonas or mycobacterial exemplars.
ImuA is an ATPase, with ATPase activity enhanced in the presence of DNA.
PMID:34190612
ImuA Facilitates SOS Mutagenesis by Inhibiting RecA-Mediated Activity in Myxococcus xanthus.
Myxococcus ImuA interacts with RecA1 and suppresses its recombinase activity. The study did not detect ImuA DNA binding; the later positive assay must be interpreted with this negative result rather than erasing it.
PMID:37530405
Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome.
M. smegmatis live-cell recruitment and biochemical evidence support an ImuB clamp-associated assembly role. Co-localization alone does not establish an active complete mutasome or native M. tuberculosis dynamics.
PMID:39706264
The RecA-NT homology motif in ImuB mediates the interaction with ImuA', which is essential for DNA damage-induced mutagenesis.
M. smegmatis ImuA′-ImuB structural and biochemical work refines accessory-complex assembly; organism-specific structure and functional tests do not establish universal ImuA-family ATPase chemistry.
PMID:30916324
New insights into the structures and interactions of bacterial Y-family DNA polymerases.
Computational comparative analysis distinguishes Y-family catalytic proteins from inactive ImuB and predicts interaction relationships. Predictions are not direct complex measurements.
PMID:41728957
Diversity and distribution of bacterial DNA polymerases.
Large comparative polymerase survey supports distinguishing DnaE2 from DnaE1/DnaE3/PolC and reports variable proofreading signatures. Predicted assemblies and genome co-occurrence do not prove complete cassette capacity.

Scope. CONCRETE denotes this specific, family-grounded bacterial realization, not a single species. Bacteria is an envelope for a patchy distribution. Complete cassette function is supported in Caulobacter, pseudomonads and mycobacteria; individual Myxococcus accessory-protein assays provide additional mechanistic comparison. Co-occurrence, a polymerase fold or a predicted complex does not establish a complete active cassette in an arbitrary genome. Accessory proteins. ImuA and actinobacterial ImuA′ are modeled as distinct family realizers of one accessory role. Their divergent sequence classifications do not establish non-homology of every structural component. The earlier universal no-activity claim is contradicted by PMID:38591662: purified Myxococcus ImuA binds DNA and hydrolyzes ATP. This does not grant those activities to Caulobacter/Pseudomonas ImuA or mycobacterial ImuA′. The 2021 Myxococcus study did not detect DNA binding; the 2024 study discusses the assay dependence of that result. Its ImuB experiments used a truncated protein, and its proposed trimeric mutasome and ATP-dependent assembly cycle remain models. Assay organisms. PMID:20615954 combines M. tuberculosis deletion genetics and yeast two-hybrid assays of its proteins with M. smegmatis individual accessory deletion, catalytic and clamp-dependent functional tests. PMID:37530405 and PMID:39706264 add M. smegmatis imaging and purified-complex evidence. These cannot be relabeled as native M. tuberculosis dynamics or stoichiometry. Process scope. GO:0019985 translesion synthesis encompasses condition-dependent mutational output. P. putida DnaE2 suppresses stationary-phase base substitutions in PMID:17331811, while PMID:28118378 finds ImuC-dependent induced mutagenesis. Neither observation cancels the other. QuickGO is_a/part_of closure places translesion synthesis under GO:0006260 DNA replication; absence of a housekeeping replicase role does not make that broad process false. Capacity boundary. Effector-cassette checks assume compatible host clamp/replication machinery and active proteins. Optional regulatory nodes do not establish native expression, RecA/LexA-independent induction, or autonomous purified lesion bypass. Regulation. RecA and LexA are optional because induction and paralog assignment vary. KT2440 LexA2 regulates a local damage-response cassette; a narrower regulon alone does not exclude SOS participation. No universal cassette-specific LexA paralog or directly measured cleavage reaction is inferred from family membership.

9Nodes
5Parts
1Variant Sets
3Variants
7Annotons
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.

Function consistency and core coverage

9 gene-function check(s) reflected in core functions · 0 conflict(s) · 4 evidence or coverage gap(s) (16 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
reca_damage_sensor recA (PSEPK)
UniProtKB:Q88ME4
Family Representative 		ATP-dependent DNA damage sensor activity
GO:0140664 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
lexa_cassette_repressor lexA2 (PSEPK)
UniProtKB:P59479
Family Representative 		DNA-binding transcription repressor activity
GO:0001217 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
myxococcus_imua_atpase MXAN_3991 / imuA (MYXXD)
UniProtKB:Q1D5A2
Family Representative 		ATP hydrolysis activity
GO:0016887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
imub_accessory_protein imuB (CAUVC)
UniProtKB:Q9A3J2
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
imub_accessory_protein Rv3394c (MYCTU)
UniProtKB:O50419
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
imub_accessory_protein imuB (PSEPK)
UniProtKB:Q88I83
Family Representative 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnae2_polymerase dnaE2 (MYCTU)
UniProtKB:P9WNT5
Family Representative 		DNA-directed DNA polymerase activity
GO:0003887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnae2_polymerase dnaE2 (CAUVC)
UniProtKB:Q9A3J3
Family Representative 		DNA-directed DNA polymerase activity
GO:0003887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnae2_polymerase dnaE2 (PSEPK)
UniProtKB:Q88I82
Family Representative 		DNA-directed DNA polymerase activity
GO:0003887 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
reca_damage_sensor bacterial RecA family
PANTHER:PTHR45900
Family 		ATP-dependent DNA damage sensor activity
GO:0140664 		Family Function Unreviewed
Family review leaves GO:0140664 UNRESOLVED. GO0140664 requires recognition of toxic DNA structures and initiation of an ATP-hydrolysis-driven signaling response. Canonical bacterial RecA, including the P. putida exemplar, has independently supported damage sensing/LexA activation. That does not establish family-wide applicability. ImuA Q1D5A2 binds DNA, hydrolyzes ATP and inhibits RecA1, but neither inhibition of RecA1 nor DNA-stimulated ATP turnover demonstrates ImuA initiation of LexA co-protease signaling. The available assays do not establish absence of such activity either. SF1 contains both canonical RecA and ImuA, and no curated residue rule resolves the distinction, so neither a subfamily-wide grant nor a negative member exception is justified. Assess each member from its functional evidence; Q1D5A2 has no supported PAINT leaf placement in the cached tree.
lexa_cassette_repressor LexA repressor family
PANTHER:PTHR33516
Family 		DNA-binding transcription repressor activity
GO:0001217 		Family Supported
Family review supports GO:0001217 FAMILY_WIDE. Repression through a winged-helix DNA-binding domain is the defining activity of the family, holds for principal repressors and narrow-regulon paralogs alike, and is experimentally established for the module's exemplar. The bacterial_imuabc_damage_induced_mutagenesis module asserts this activity for its LexA gate annoton on that basis.
myxococcus_imua_atpase characterized Myxococcus ImuA accessory proteins
Family 		ATP hydrolysis activity
GO:0016887 		Family Id Missing
The family has no identifier linking it to a curated family review.
imub_accessory_protein ImuB catalytically inactive UmuC-fold adaptors
Pfam:PF00817
Family 		protein-macromolecule adaptor activity
GO:0030674 		Family Review Missing
No supported structured family review is available for Pfam:PF00817.
imub_accessory_protein ImuB catalytically inactive UmuC-fold adaptors
PANTHER:PTHR35369:SF2
Family 		protein-macromolecule adaptor activity
GO:0030674 		Family Supported
Family review supports GO:0030674 for PANTHER:PTHR35369:SF2. The adaptor activity is the ImuB role and is established for the mycobacterial member by two-hybrid interactions with ImuA', DnaE1, DnaE2 and the beta clamp plus a clamp-binding allele that abolishes function. It is asserted for SF2 only. It is not claimed for the ImuA proteins of SF3, for which no molecular activity has been demonstrated at all, and not for the SulA inhibitors of SF4, whose FtsZ binding is an inhibitory interaction rather than an adaptor function. The bacterial_imuabc_damage_induced_mutagenesis module asserts this activity for its ImuB annoton on this basis.
dnae2_polymerase DnaE2 damage-inducible type-C polymerases
InterPro:IPR023073
Family 		DNA-directed DNA polymerase activity
GO:0003887 		Family Review Missing
No supported structured family review is available for InterPro:IPR023073.
dnae2_polymerase DnaE2 damage-inducible type-C polymerases
PANTHER:PTHR32294:SF4
Family 		DNA-directed DNA polymerase activity
GO:0003887 		Family Supported
Family review supports GO:0003887 FAMILY_WIDE. Templated nucleotidyl transfer is the defining chemistry of the type-C fold and is asserted for every subfamily, including the error-prone SF4, whose catalytic residues are retained and functionally required. The bacterial_imuabc_damage_induced_mutagenesis module asserts this activity for its DnaE2 annoton on that basis.

Feedback loops (advisory, prose-driven: a regulator counts as "feedback" when its own description says so)

✓ every negative regulator described as feedback has an upstream edge closing the loop.

  • lexa_cassette_gate ⊣ imua_accessory [closed]
    lexa_cassette_gate is regulated by reca_damage_signal: feedback loop closed

Gene-review completeness (12/12 grounded genes reviewed)

12 complete review(s) · 4 with deep research · 0 missing review · 8 reviewed but lacking deep research

Gene Review Complete Deep research
dnaE2 P9WNT5 ✓ ✓ ✗
dnaE2 Q88I82 ✓ ✓ ✓
dnaE2 Q9A3J3 ✓ ✓ ✗
imuA Q9A3J1 ✓ ✓ ✗
imuB Q88I83 ✓ ✓ ✓
imuB Q9A3J2 ✓ ✓ ✗
lexA2 P59479 ✓ ✓ ✓
MXAN_3991 Q1D5A2 ✓ ✓ ✗
PP_3117 Q88I84 ✓ ✓ ✗
recA Q88ME4 ✓ ✓ ✓
Rv3394c O50419 ✓ ✓ ✗
Rv3395c P9WKZ9 ✓ ✓ ✗

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. Applying this to a particular cassette repressor, such as KT2440 LexA2, is a family-level inference rather than a direct cleavage result for that paralog.
lexa_cassette_gate -> imua_accessory Negatively Regulates
Cassette-associated LexA can repress effector transcription in characterized regulons. Organization, paralog identity and induction timing vary by lineage; neither synchronous induction nor one operon is required by this module.
imua_accessory -> imub_recruitment Provides Input For
The accessory protein interacts with the ImuB-centered assembly. This functional dependency does not assert a universal temporal order of partner recruitment. M. tuberculosis proteins were tested by yeast two-hybrid, and M. smegmatis purified-complex evidence resolves a specific assembly interface.
ImuB recruits DnaE2 and, through the beta clamp, mediates its access to the replication fork at the damaged template.
Part 1: RecA-dependent DNA-damage signaling (optional)
activated RecA damage signalBiological Processreca_damage_signal
PMID:36288458
Sending out an SOS - the bacterial DNA damage response.
Comparative SOS review documents lineage-specific regulons and alternative TLS systems, supporting optional RecA/LexA context and taxon-specific cassette assessment.

Annotons

RecA nucleoprotein damage sensor
reca_damage_sensor
Participant: Family: bacterial RecA family
Family:
bacterial RecA familyPANTHER:PTHR45900
Representative Members: recA (PSEPK)UniProtKB: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
PMID:36288458
Sending out an SOS - the bacterial DNA damage response.
Comparative SOS review documents lineage-specific regulons and alternative TLS systems, supporting optional RecA/LexA context and taxon-specific cassette assessment.

Annotons

cassette-specific LexA repressor
lexa_cassette_repressor
Participant: Family: LexA repressor family
Family:
LexA repressor familyPANTHER:PTHR33516
Representative Members: lexA2 (PSEPK)UniProtKB: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-type accessory function
accessory step of the mutagenesis cassetteBiological Processimua_accessory

An accessory protein works with ImuB. Distinct ImuA and ImuA′ family realizers are retained. Molecular activity is assigned only where demonstrated for a specific carrier, not from the shared accessory role alone.

Variant set: Characterized ImuA-type accessory realizers by lineage-specific accessory protein family [Realizer] (Exactly One)
PMID:15886391
ImuA homologs are absent from Actinomycetales, where genomic context points to a RecA-like protein instead.
Although proteins with significant similarity to ImuA cannot be found in Actinomycetales, the genomic context analysis suggests that the RecA-like protein encoded by M.tuberculosis Rv3395 may represent a functional counterpart of ImuA in these organisms.
PMID:20615954
The actinobacterial carrier is a protein of unknown function restricted largely to actinomycetes, designated ImuA'.
which encodes a protein of unknown function restricted primarily to actinomycetes

Alternative family realizers of one accessory role. The sequence/domain groupings are kept separate; this modeling choice does not assert independent evolutionary origin of their shared RecA-like structural features.

proteobacterial ImuABiological Processimua_proteobacterial

Annotons

ImuA translesion-synthesis accessory protein
imua_accessory_protein
Participant: Family: ImuA accessory proteins of the imuA-imuB-dnaE2 cassette
Family:
ImuA accessory proteins of the imuA-imuB-dnaE2 cassette Split across two InterPro families that do not correspond to one PANTHER subfamily, so no PANTHER id is asserted: Pseudomonas ImuA carries IPR047610 and PANTHER PTHR35369:SF3, Caulobacter ImuA carries IPR017026 and has no PANTHER assignment.
Representative Members: imuA (CAUVC)UniProtKB:Q9A3J1 PP_3117 (PSEPK)UniProtKB:Q88I84

Processes

translesion synthesisGO:0019985

Accessory cassette component needed for effective DnaE2-dependent synthesis. The current Caulobacter and Pseudomonas exemplars do not have a directly established molecular activity.

PMID:15886391
Deletion of the Caulobacter imuA ortholog establishes a requirement in damage tolerance, complemented by the wild-type allele.
The genes imuA and imuB encode previously uncharacterized proteins, which are shown here for the first time to be involved in DNA damage tolerance.
file:PSEPK/PP_3117/PP_3117-uniprot.txt
Q88I84 carries the ImuA-specific IPR047610 family and the NCBIfam ImuA_translesion model.
DR NCBIfam; NF033429; ImuA_translesion; 1.
PMID:38591662
Myxococcus xanthus translesion DNA synthesis protein ImuA is an ATPase enhanced by DNA.
Purified Myxococcus ImuA has DNA-enhanced ATPase activity and DNA binding. These tested activities invalidate a universal no-activity statement, but do not establish the same activities in the existing Caulobacter, Pseudomonas or mycobacterial exemplars.
ImuA is an ATPase, with ATPase activity enhanced in the presence of DNA.
PMID:34190612
ImuA Facilitates SOS Mutagenesis by Inhibiting RecA-Mediated Activity in Myxococcus xanthus.
Myxococcus ImuA interacts with RecA1 and suppresses its recombinase activity. The study did not detect ImuA DNA binding; the later positive assay must be interpreted with this negative result rather than erasing it.

The 2024 Myxococcus ImuA ATPase and DNA-binding results resolve the former universal knowledge gap but do not directly establish these activities for Q9A3J1 or Q88I84. The separately modeled Myxococcus realizer encodes the measured activity without transferring it to these exemplars.

biochemically characterized Myxococcus ImuABiological Processmyxococcal_imua

Annotons

DNA-stimulated ATPase activity of Myxococcus ImuA
myxococcus_imua_atpase
Participant: Family: characterized Myxococcus ImuA accessory proteins
Family:
characterized Myxococcus ImuA accessory proteins A function-qualified accessory group anchored to the experimentally studied DK1622 protein. No family identifier is asserted for this precise role. Q1D5A2 belongs to broad PANTHER PTHR45900:SF1, but that classification alone establishes neither ImuA accessory function nor canonical RecA recombinase or SOS-sensor function.
Representative Members: MXAN_3991 / imuA (MYXXD)UniProtKB:Q1D5A2
Required Function:
ATP hydrolysis activityGO:0016887

Function

ATP hydrolysis activityGO:0016887

Processes

error-prone translesion synthesisGO:0042276

ImuA accessory participation in mutagenic lesion bypass, with DNA-stimulated ATPase activity demonstrated for this representative. The biochemical coupling between these observations is unresolved.

PMID:34190612
DK1622 ImuA contributes to induced mutagenesis and inhibits RecA1-mediated recombination. The imuA deletion reduces mutagenesis without reproducing complete ImuB/DnaE2 loss; accessory participation does not imply absolute indispensability for every bypass event.
PMID:38591662
DNA binding, ATP hydrolysis and interaction with N-terminally truncated ImuB were tested. ATP-controlled assembly/disassembly remains a proposed model, and the ImuB construct is not full-length native ImuB. The earlier negative DNA-binding assay is retained in the review.
file:analysis/module_audits/bacterial_imuabc_damage_induced_mutagenesis/myxococcus-consultation/RESULTS.md
Primary sequence mapping independently identifies the 2021 DK1622 locus and distinguishes direct identity verification from the inferred connection to the 2024 biochemical construct.
The ImuA assayed in the 2021 DK1622 study is MXAN_3991, encoding ABF92318.1 / UniProt Q1D5A2.

This branch adds one characterized accessory realizer, not a reviewed complete Myxococcus cassette. A mixed-species list of accessory and polymerase hits does not establish an assembly. ATPase qualification identifies the characterized activity-bearing realizer; failing that qualification does not prove that an ATPase-deficient protein cannot support any TLS.

actinobacterial ImuA'Biological Processimua_prime_actinobacterial

Annotons

ImuA' translesion-synthesis accessory protein
imua_prime_accessory_protein
Participant: Family: actinobacterial ImuA' accessory proteins
Family:
actinobacterial ImuA' accessory proteins Actinobacterial ImuA′ accessory proteins with a RecA-like fold and a distinct sequence/domain classification from the listed ImuA families. No unified PANTHER family is established here; a molecular activity is not inferred from fold similarity.
Representative Members: Rv3395c (MYCTU)UniProtKB:P9WKZ9

Processes

translesion synthesisGO:0019985

Actinobacterial accessory realizer required for cassette function and interacting with ImuB. New M. smegmatis complex evidence is kept separate from target-specific M. tuberculosis catalytic activity.

PMID:20615954
The paper combines M. tuberculosis cassette genetics with M. smegmatis individual-deletion experiments. Its aggregate conclusion supports the ImuA′ accessory role without making every single-gene assay native to M. tuberculosis.
Here, we confirm that Rv3395c (designated imuA ′) and Rv3394c ( imuB ) are individually essential for induced mutagenesis and damage tolerance.
PMID:20615954
ImuA' binds ImuB directly through the C-terminal regions of both proteins and does not self-associate like RecA.
We observed the direct interaction of ImuA′ with ImuB involving the C-terminal regions of both proteins; however, no evidence of ImuA′ self-association was detected that might indicate RecA-like filamentation ( 40 ).
PMID:37530405
Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome.
M. smegmatis live-cell recruitment and biochemical evidence support an ImuB clamp-associated assembly role. Co-localization alone does not establish an active complete mutasome or native M. tuberculosis dynamics.
PMID:39706264
The RecA-NT homology motif in ImuB mediates the interaction with ImuA', which is essential for DNA damage-induced mutagenesis.
M. smegmatis ImuA′-ImuB structural and biochemical work refines accessory-complex assembly; organism-specific structure and functional tests do not establish universal ImuA-family ATPase chemistry.

No ATPase activity is transferred from Myxococcus ImuA. M. smegmatis structural/biochemical evidence establishes an ImuA′-ImuB complex, not that M. tuberculosis ImuA′ catalyzes nucleotide hydrolysis. Target-specific localization remains separately assessed in the gene review.

Part 4: ImuB polymerase-recruitment scaffold
ImuB recruitment stepBiological Processimub_recruitment

Annotons

ImuB translesion-synthesis accessory protein
imub_accessory_protein
Participant: Family: ImuB catalytically inactive UmuC-fold adaptors
Family:
ImuB catalytically inactive UmuC-fold adaptorsPfam:PF00817 UmuC/Y-family folds that have lost the catalytic carboxylates. The Pfam IMS domain is the primary grounding; the PANTHER subfamily is given as well, since the PTHR35369 family itself also contains the SulA cell-division inhibitors.
Representative Members: imuB (CAUVC)UniProtKB:Q9A3J2 Rv3394c (MYCTU)UniProtKB:O50419 imuB (PSEPK)UniProtKB:Q88I83
Required Function:
protein-macromolecule adaptor activityGO:0030674

Function

protein-macromolecule adaptor activityGO:0030674
Targets: ImuA-type accessory protein DnaE2 error-prone polymerase DNA polymerase III beta sliding clamp

Processes

translesion synthesisGO:0019985

Catalytically inactive polymerase-like adaptor that recruits DnaE2 and tethers the complex to the replication clamp at damaged DNA.

PMID:30916324
New insights into the structures and interactions of bacterial Y-family DNA polymerases.
Computational comparative analysis distinguishes Y-family catalytic proteins from inactive ImuB and predicts interaction relationships. Predictions are not direct complex measurements.
PMID:37530405
Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome.
M. smegmatis live-cell recruitment and biochemical evidence support an ImuB clamp-associated assembly role. Co-localization alone does not establish an active complete mutasome or native M. tuberculosis dynamics.
PMID:39706264
The RecA-NT homology motif in ImuB mediates the interaction with ImuA', which is essential for DNA damage-induced mutagenesis.
M. smegmatis ImuA′-ImuB structural and biochemical work refines accessory-complex assembly; organism-specific structure and functional tests do not establish universal ImuA-family ATPase chemistry.
Part 5: DnaE2-dependent damage-tolerant DNA synthesis
DnaE2 lesion-bypass DNA synthesisBiological Processdnae2_mutagenic_synthesis

Annotons

DnaE2 error-prone DNA polymerase
dnae2_polymerase
Participant: Family: DnaE2 damage-inducible type-C polymerases
Family:
DnaE2 damage-inducible type-C polymerasesInterPro:IPR023073 Second, non-essential copies of the DNA polymerase III alpha subunit. The InterPro family is the primary grounding; the PANTHER subfamily separates them from the replicative DnaE and PolC subfamilies of PTHR32294. No PAINT ancestral node is asserted for this role: the only IBD node in PTHR32294 (PTN000793159, polymerase activity) is seeded by E. coli DnaE rather than by any DnaE2, and it is adjudicated in that family's review instead.
Representative Members: dnaE2 (MYCTU)UniProtKB:P9WNT5 dnaE2 (CAUVC)UniProtKB:Q9A3J3 dnaE2 (PSEPK)UniProtKB: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; the mutational output is usually but not invariably mutagenic.

PMID:21475246
Breaking the rules: bacteria that use several DNA polymerase IIIs.
Narrative review distinguishing bacterial C-family replicases from the damage-induced ImuC system. Polymerase fold does not identify which replication role a member performs.
Yet another group of bacteria encode a second Pol III (ImuC)
PMID:41728957
Diversity and distribution of bacterial DNA polymerases.
Large comparative polymerase survey supports distinguishing DnaE2 from DnaE1/DnaE3/PolC and reports variable proofreading signatures. Predicted assemblies and genome co-occurrence do not prove complete cassette capacity.
PMID:28118378
DNA Polymerases ImuC and DinB Are Involved in DNA Alkylation Damage Tolerance in Pseudomonas aeruginosa and Pseudomonas putida.
Pseudomonas ImuC/DnaE2 contributes to alkylation-damage tolerance and induced mutagenesis. These outcomes differ from the stationary-phase base-substitution assay and prevent interpreting its antimutator result as a universal absence of mutagenic function.
polymerases ImuC and DinB ensured a protective role against N- and O-methylation