MutH-independent bacterial DNA mismatch repair

A reusable four-stage bacterial module in which MutS recognizes a replication mismatch, the beta sliding clamp helps orient an endonuclease-bearing MutL that nicks DNA without MutH, and a helicase, single-stranded DNA-binding protein, and one or more directional exonucleases remove the error-containing tract before DNA polymerase and ligase restore the duplex. The module is explicitly distinct from the Dam/MutH-directed Escherichia coli route. Mismatch avoidance by polymerase proofreading, recombination control, and the other repair pathways that share UvrD, RecJ, polymerase, or ligase are outside the boundary.

MODULE:muth_independent_mismatch_repairDRAFTBiological Processmodules/muth_independent_mismatch_repair.yaml

mismatch repairGO:0006298

GO:0006298

mismatch repair

GO:0006298 defines the biological process represented by the module.

PMID:31599106

Mismatch repair hierarchy of Pseudomonas putida revealed by mutagenic ssDNA recombineering of the pyrF gene.

Direct KT2440 genetics establishes MutS- and MutL-dependent correction and the absence of a canonical MutH component.

PMID:23969026

Analysis of DNA structure and sequence requirements for Pseudomonas aeruginosa MutL endonuclease activity.

Direct biochemistry establishes duplex-DNA nicking by the close Pseudomonas MutL exemplar Q9HUL8.

file:PSEPK/mutL/mutL-bioinformatics/RESULTS.md

Reproducible Q88DD1-Q9HUL8 MutL global protein alignment

Retained inputs, scripts, parameters, checksums, and outputs establish 521 identical residues among 627 aligned residue pairs (83.0941%).

PMID:30292721

Involvement of transcription-coupled repair factor Mfd and DNA helicase UvrD in mutational processes in Pseudomonas putida.

Direct P. putida genetics supports an important but partially redundant UvrD contribution to mismatch repair.

PANTHER:PTN002260821

MutS TreeGrafter support node

Current PSEPK GOA uses this exact node for MutS annotations.

PANTHER:PTN002225929

MutL TreeGrafter support node

Current PSEPK GOA uses this exact node for MutL annotations.

PANTHER:PTN008511651

UvrD TreeGrafter support node

Current PSEPK GOA uses this exact node for UvrD annotations.

PANTHER:PTN002437006

XseB TreeGrafter support node

Current PSEPK GOA uses this exact node for XseB annotations.

PANTHER:PTHR30478

DNA polymerase III beta sliding clamp family

PSEPK DnaN P0A120 and E. coli DnaN P0A988 are exact representatives of the beta-clamp role.

PANTHER:PTHR10302

bacterial single-stranded DNA-binding protein family

PSEPK SSB Q88QK5 and E. coli SSB P0AGE0 are exact representatives of the ssDNA-binding and repair-partner scaffold role.

file:PSEPK/mutS/mutS-ai-review.yaml

PSEPK mutS gene review

Q88ME7 supplies ATP-dependent mismatch recognition.

file:PSEPK/mutL/mutL-ai-review.yaml

PSEPK mutL gene review

Q88DD1 supplies ATP-dependent coordination and inferred strand incision.

file:PSEPK/uvrD/uvrD-ai-review.yaml

PSEPK uvrD gene review

Q88C31 supplies a directly supported but nonexclusive repair helicase.

file:PSEPK/xseA/xseA-ai-review.yaml

PSEPK xseA gene review

Q88P26 supplies the Exonuclease VII large subunit candidate.

file:PSEPK/xseB/xseB-ai-review.yaml

PSEPK xseB gene review

Q88QG5 supplies the Exonuclease VII small subunit candidate.

file:PSEPK/sbcB/sbcB-ai-review.yaml

PSEPK sbcB gene review

Q88N51 supplies the 3'-to-5' Exonuclease I candidate.

file:PSEPK/recJ/recJ-ai-review.yaml

PSEPK recJ gene review

Q88MU1 supplies the 5'-to-3' RecJ candidate.

12Nodes

8Parts

1Variant Sets

3Variants

11Annotons

5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:muth_independent_mismatch_repair deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

mismatch_recognition → mutl_incision [NOT_CHECKED]

Gene-review completeness (7/22 grounded genes reviewed)

7 complete review(s) · 7 with deep research · 15 missing review · 0 reviewed but lacking deep research

Gene	Review	Complete	Deep research
mutL Q88DD1	✓	✓	✓
mutS Q88ME7	✓	✓	✓
Escherichia coli UvrD P03018	✗	—	—
Escherichia coli XseA P04994	✗	—	—
Escherichia coli SbcB P04995	✗	—	—
PSEPK DnaN P0A120	✗	—	—
Escherichia coli XseB P0A8G9	✗	—	—
Escherichia coli DnaN P0A988	✗	—	—
Escherichia coli SSB P0AGE0	✗	—	—
Escherichia coli DnaE P10443	✗	—	—
Escherichia coli LigA P15042	✗	—	—
Escherichia coli RecJ P21893	✗	—	—
Escherichia coli MutS P23909	✗	—	—
PSEPK LigA Q88F25	✗	—	—
PSEPK DnaE Q88MG5	✗	—	—
PSEPK SSB Q88QK5	✗	—	—
Pseudomonas aeruginosa MutL Q9HUL8	✗	—	—
recJ Q88MU1	✓	✓	✓
sbcB Q88N51	✓	✓	✓
uvrD Q88C31	✓	✓	✓
xseA Q88P26	✓	✓	✓
xseB Q88QG5	✓	✓	✓

Tree

MutH-independent bacterial DNA mismatch repairBiological Processmuth_independent_mismatch_repair

Parts
1. 1. mismatch recognition
2. MutS-dependent mismatch recognitionMolecular Functionmismatch_recognition
  
  Annotons
  - ATP-dependent MutS mismatch sensor Family: bacterial MutS mismatch sensors
3. 2. MutL-dependent strand incision
4. MutL coordination and duplex-DNA nickingBiological Processmutl_incision
  
  Annotons
  - MutL ATPase coordinator Family: MutL-family ATPase coordinators
  - MutL strand-incision endonuclease Family: endonuclease-bearing bacterial MutL proteins
  - Replication beta-clamp incision context Family: bacterial beta sliding clamps
5. 3. mismatch-containing tract excision
6. Directional unwinding and exonucleolytic excisionMetabolic Pathwaymismatch_excision
  
  Annotons
  - Single-stranded DNA-binding repair scaffold Family: bacterial single-stranded DNA-binding proteins
  Parts
  1. 1. repair-directed DNA unwinding
  2. UvrD/PcrA-family repair helicaseReactionrepair_helicase_unwinding
    
    Annotons
    
    3'-to-5' DNA helicase Family: UvrD/PcrA-family DNA helicases
  3. 2. directional single-stranded DNA degradation
  4. Orientation-dependent mismatch-excision nucleasesMetabolic Pathwayexcision_nuclease_choice
    
    Variants
    
    Directional exonuclease implementations by nick orientation and nuclease availability (One Or More)
    
    Exonuclease I 3'-to-5' routeReactionexoi_3_to_5_excision
    
    Annotons
    
    Single-stranded DNA 3'-to-5' Exonuclease I Family: bacterial Exonuclease I proteins
    
    RecJ 5'-to-3' routeReactionrecj_5_to_3_excision
    
    Annotons
    
    RecJ 5'-to-3' exonuclease Family: bacterial RecJ exonucleases
    
    Exonuclease VII bidirectional routeProtein Complexexonuclease_vii_bidirectional_excision
    
    Annotons
    
    XseA/XseB Exonuclease VII Protein Complex: bacterial Exonuclease VII
7. 4. repair synthesis and strand sealing
8. DNA gap filling and ligationMetabolic Pathwayrepair_synthesis_and_sealing
  
  Parts
  1. 1. repair DNA synthesis
  2. DNA polymerase-dependent gap fillingReactionrepair_gap_filling
    
    Annotons
    
    DNA-directed DNA polymerase Family: bacterial replicative DNA polymerase catalytic subunits
  3. 2. nick sealing
  4. NAD-dependent DNA ligationReactionrepair_nick_ligation
    
    Annotons
    
    NAD-dependent DNA ligase Family: bacterial NAD-dependent DNA ligases

Details

MutH-independent bacterial DNA mismatch repairBiological Processmuth_independent_mismatch_repair

mismatch repairGO:0006298

Exact UniProt exemplars delimit every family-level role without restricting the module taxonomically or importing the MutH incision mechanism. Exonuclease I, RecJ, and Exonuclease VII are orientation-dependent alternative implementations rather than universally obligatory proteins. DnaN supplies the replisome-coupled clamp context, while SSB stabilizes the exposed excision intermediate and coordinates processing proteins. DnaN, SSB, DnaE, and LigA are shared repair and replication machinery included to complete the pathway, not MMR-specific proteins. PTNs encountered in source GOA are TreeGrafter or combined-IEA provenance only; no ancestral node is asserted without verified PAINT IBD evidence.

Connections

mismatch_recognition -> mutl_incision Precedes

Mismatch-bound MutS recruits and activates MutL.

mutl_incision -> mismatch_excision Provides Input For

MutL nicking creates the entry point for unwinding and excision.

mismatch_excision -> repair_synthesis_and_sealing Provides Input For

Excision generates the DNA gap restored by polymerase and ligase.

Part 1: mismatch recognition

MutS-dependent mismatch recognitionMolecular Functionmismatch_recognition

Annotons

ATP-dependent MutS mismatch sensor

muts_mismatch_sensor

Participant: Family: bacterial MutS mismatch sensors

Family:

bacterial MutS mismatch sensorsPANTHER:PTHR11361

Representative Members: PSEPK MutSUniProtKB:Q88ME7 Escherichia coli MutSUniProtKB:P23909

Function

ATP-dependent DNA damage sensor activityGO:0140664

Processes

mismatch repairGO:0006298

Locations

cytosolGO:0005829

Recognizes a base-pair mismatch or small insertion/deletion loop and initiates ATP-dependent recruitment of MutL.

Part 2: MutL-dependent strand incision

MutL coordination and duplex-DNA nickingBiological Processmutl_incision

Annotons

MutL ATPase coordinator

mutl_atpase

Participant: Family: MutL-family ATPase coordinators

Family:

MutL-family ATPase coordinatorsPANTHER:PTHR10073

Representative Members: PSEPK MutLUniProtKB:Q88DD1 Pseudomonas aeruginosa MutLUniProtKB:Q9HUL8

Required Function:

ATP hydrolysis activityGO:0016887

PTHR10073 also contains eukaryotic MLH/PMS proteins and MutL implementations with different incision mechanisms. Exact bacterial exemplars and the required ATPase function delimit this coordinator role.

Function

ATP hydrolysis activityGO:0016887

Processes

mismatch repairGO:0006298

Uses the GHKL ATPase cycle to coordinate the transition from MutS recognition to strand incision and excision.

MutL strand-incision endonuclease

mutl_endonuclease

Participant: Family: endonuclease-bearing bacterial MutL proteins

Family:

endonuclease-bearing bacterial MutL proteinsPANTHER:PTHR10073

Representative Members: PSEPK MutLUniProtKB:Q88DD1 Pseudomonas aeruginosa MutLUniProtKB:Q9HUL8

Required Function:

double-stranded DNA endonuclease activityGO:1990238

The broad PTHR10073 family is not itself an endonuclease selector. The required function and directly characterized Q9HUL8 exemplar restrict this role to incision-capable MutL implementations.

Function

double-stranded DNA endonuclease activityGO:1990238

Substrates: intact duplex DNA near a mismatch water

Products: nicked duplex DNA

Cofactors: divalent metal ion

Processes

mismatch repairGO:0006298

Introduces a strand discontinuity that replaces the MutH incision step of methyl-directed systems. The precise KT2440 strand-discrimination signal remains unresolved.

Replication beta-clamp incision context

dnan_beta_clamp

Participant: Family: bacterial beta sliding clamps

Family:

bacterial beta sliding clampsPANTHER:PTHR30478

Representative Members: PSEPK DnaNUniProtKB:P0A120 Escherichia coli DnaNUniProtKB:P0A988

Function

DNA polymerase processivity factor activityGO:0030337

Processes

mismatch repairGO:0006298

Provides replisome-coupled clamp context that can orient or stimulate MutL incision in MutH-independent systems; the exact strand-discrimination signal varies among lineages.

Part 3: mismatch-containing tract excision

Directional unwinding and exonucleolytic excisionMetabolic Pathwaymismatch_excision

Annotons

Single-stranded DNA-binding repair scaffold

ssb_excision_scaffold

Participant: Family: bacterial single-stranded DNA-binding proteins

Family:

bacterial single-stranded DNA-binding proteinsPANTHER:PTHR10302

Representative Members: PSEPK SSBUniProtKB:Q88QK5 Escherichia coli SSBUniProtKB:P0AGE0

Function

single-stranded DNA bindingGO:0003697

Processes

mismatch repairGO:0006298

Coats exposed single-stranded DNA and recruits or coordinates DNA-processing partners during tract unwinding and degradation.

Connections

repair_helicase_unwinding -> excision_nuclease_choice Provides Input For

Helicase-generated single-stranded DNA is degraded by an available exonuclease route.

Part 1: repair-directed DNA unwinding

UvrD/PcrA-family repair helicaseReactionrepair_helicase_unwinding

Annotons

3'-to-5' DNA helicase

uvrD_repair_helicase

Participant: Family: UvrD/PcrA-family DNA helicases

Family:

UvrD/PcrA-family DNA helicasesPANTHER:PTHR11070

Representative Members: PSEPK UvrDUniProtKB:Q88C31 Escherichia coli UvrDUniProtKB:P03018

Required Function:

3'-5' DNA helicase activityGO:0043138

PTHR11070 also contains RecB, PcrA, and Srs2-like helicases. Exact UvrD exemplars plus the required directional DNA-helicase function delimit this role.

Function

3'-5' DNA helicase activityGO:0043138

Substrates: nicked duplex DNA ATP water

Products: unwound DNA repair intermediate ADP phosphate proton

Processes

mismatch repairGO:0006298

Unwinds from the repair nick toward and beyond the mismatch. PSEPK genetics shows that Q88C31 contributes strongly but that residual MMR remains without it.

Part 2: directional single-stranded DNA degradation

Orientation-dependent mismatch-excision nucleasesMetabolic Pathwayexcision_nuclease_choice

One or more directional exonucleases degrade the displaced error-containing strand. Which candidates dominate each orientation in KT2440 is not directly resolved.

Variant set: Directional exonuclease implementations by nick orientation and nuclease availability (One Or More)

Exonuclease I 3'-to-5' routeReactionexoi_3_to_5_excision

Annotons

Single-stranded DNA 3'-to-5' Exonuclease I

sbcB_exonuclease

Participant: Family: bacterial Exonuclease I proteins

Family:

bacterial Exonuclease I proteinsPANTHER:PTHR11046:SF11

Representative Members: PSEPK SbcBUniProtKB:Q88N51 Escherichia coli SbcBUniProtKB:P04995

Function

single-stranded DNA 3'-5' DNA exonuclease activityGO:0008310

Provides 3'-to-5' degradation of an exposed single-stranded repair tract.

RecJ 5'-to-3' routeReactionrecj_5_to_3_excision

Annotons

RecJ 5'-to-3' exonuclease

recJ_exonuclease

Participant: Family: bacterial RecJ exonucleases

Family:

bacterial RecJ exonucleasesPANTHER:PTHR30255

Representative Members: PSEPK RecJUniProtKB:Q88MU1 Escherichia coli RecJUniProtKB:P21893

Function

single-stranded DNA 5'-3' DNA exonuclease activityGO:0045145

Provides 5'-to-3' degradation of an exposed single-stranded repair tract.

Exonuclease VII bidirectional routeProtein Complexexonuclease_vii_bidirectional_excision

Annotons

XseA/XseB Exonuclease VII

xseAB_exonuclease_vii

Participant: Protein Complex: bacterial Exonuclease VII

Protein Complex:

bacterial Exonuclease VIIGO:0009318

Active units:

Exonuclease VII large subunit

Participant: Family: XseA large subunits

Family:

XseA large subunitsPANTHER:PTHR30008

Representative Members: PSEPK XseAUniProtKB:Q88P26 Escherichia coli XseAUniProtKB:P04994

Role: Catalytic large subunit of the heterooligomer.

Exonuclease VII small subunit

Participant: Family: XseB small subunits

Family:

XseB small subunitsPANTHER:PTHR34137

Representative Members: PSEPK XseBUniProtKB:Q88QG5 Escherichia coli XseBUniProtKB:P0A8G9

Role: Small subunit required for the heterooligomeric enzyme.

Function

exodeoxyribonuclease VII activityGO:0008855

Provides bidirectional single-stranded DNA degradation through the XseA/XseB complex.

Part 4: repair synthesis and strand sealing

DNA gap filling and ligationMetabolic Pathwayrepair_synthesis_and_sealing

Connections

repair_gap_filling -> repair_nick_ligation Provides Input For

Gap filling leaves a nick that is sealed by DNA ligase.

Part 1: repair DNA synthesis

DNA polymerase-dependent gap fillingReactionrepair_gap_filling

Annotons

DNA-directed DNA polymerase

dna_polymerase_repair_synthesis

Participant: Family: bacterial replicative DNA polymerase catalytic subunits

Family:

bacterial replicative DNA polymerase catalytic subunitsPANTHER:PTHR32294

Representative Members: PSEPK DnaEUniProtKB:Q88MG5 Escherichia coli DnaEUniProtKB:P10443

Function

DNA-directed DNA polymerase activityGO:0003887

Fills the excision-generated single-stranded gap using the intact strand as template.

Part 2: nick sealing

NAD-dependent DNA ligationReactionrepair_nick_ligation

Annotons

NAD-dependent DNA ligase

ligA_repair_ligation

Participant: Family: bacterial NAD-dependent DNA ligases

Family:

bacterial NAD-dependent DNA ligasesPANTHER:PTHR23389

Representative Members: PSEPK LigAUniProtKB:Q88F25 Escherichia coli LigAUniProtKB:P15042

Function

DNA ligase (NAD+) activityGO:0003911

Seals the remaining nick after repair synthesis.