Bacterial chromosomal DNA replication

Bacterial chromosome duplication coordinates origin recognition and helicase loading with template unwinding, protection and priming, replicative synthesis and proofreading, clamp-dependent processivity, RNA-primer replacement, nick sealing and topological separation. Alternative loader and polymerase architectures are grounded in Proteobacteria, Bacillota and Actinomycetota examples.

MODULE:bacterial_chromosomal_dna_replicationCOMPLETECONCRETEBiological Processmodules/bacterial_chromosomal_dna_replication.yaml

DNA replicationGO:0006260

PMID:22206257

Architecture and conservation of the bacterial DNA replication machinery, an underexploited drug target.

The older review distinguishes widespread core replication machinery from lineage-restricted modules.

Other modules are restricted to particular phylogenetic groups and are likely therefore to have evolved more recently

PMID:41728957

Diversity and distribution of bacterial DNA polymerases.

Three major replicative catalytic-subunit configurations are DnaE1 alone, PolC with DnaE1, and PolC with DnaE3.

(i) DnaE1-only, (ii) PolC + DnaE1, and (iii) PolC + DnaE3

The boundary is DnaA-initiated duplication with a circular-chromosome topology realization. Bacteria denotes reusable scope, not universal possession of every named enzyme. Missing representatives or unresolved physiological roles are gaps in this panel, not organismal absence. Every role must be evaluated within a compatible lineage; representatives from different species cannot be pooled to claim a native complete pathway. Domain or broad-family membership alone does not establish DnaE1/3 identity, PHP catalysis, cargo-independent assembly or a complete loader/topoisomerase. Tus/Rtp fork traps, dimer resolution and lesion bypass are conditional adjacent mechanisms. HolC/HolD and tau coupling are explicit contextual roles; their optional status does not assert physiological dispensability in each species. The former exclusion of primer replacement and the PP_0978 HolD assignment are superseded. No PP_1552 DnaC/DciA claim is retained.

30Nodes

14Parts

6Variant Sets

15Variants

32Annotons

6Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:bacterial_chromosomal_dna_replication 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.

Function consistency and core coverage

39 gene-function check(s) reflected in core functions · 0 conflict(s) · 21 evidence or coverage gap(s) (72 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.

Annoton	Participant	Function	Assessment
dnaa_origin_initiation_activity	dnaA (Escherichia coli K-12) UniProtKB:P03004 Family Representative	DNA replication origin binding GO:0003688	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnaa_origin_initiation_activity	dnaA (Pseudomonas putida KT2440) UniProtKB:P0A116 Family Representative	DNA replication origin binding GO:0003688	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnaa_origin_initiation_activity	dnaA (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P05648 Family Representative	DNA replication origin binding GO:0003688	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnac_helicase_loading_activity	dnaC (Escherichia coli K-12) UniProtKB:P0AEF0 Family Representative	replicative DNA helicase loader activity No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
dnad_origin_recruitment	dnaD (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P39787 Family Representative	DNA replication origin binding GO:0003688	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnab_loading_accessory	dnaB (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P07908 Family Representative	DNA binding GO:0003677	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnai_loader	dnaI (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P06567 Family Representative	ATP hydrolysis activity GO:0016887	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dcia_helicase_loading_activity	dciA (Vibrio cholerae O1 biovar El Tor str. N16961) UniProtKB:Q9KPH3 Family Representative	replicative DNA helicase loader activity No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
dnab_helicase	dnaB (Escherichia coli K-12) UniProtKB:P0ACB0 Family Representative	5'-3' DNA helicase activity GO:0043139	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnab_helicase	dnaB (Pseudomonas putida KT2440) UniProtKB:Q88DF2 Family Representative	5'-3' DNA helicase activity GO:0043139	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnab_helicase	dnaC (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P37469 Family Representative	5'-3' DNA helicase activity GO:0043139	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ssb_template_protection	ssb (Escherichia coli K-12) UniProtKB:P0AGE0 Family Representative	single-stranded DNA binding GO:0003697	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ssb_template_protection	ssb (Pseudomonas putida KT2440) UniProtKB:Q88QK5 Family Representative	single-stranded DNA binding GO:0003697	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ssb_template_protection	ssbA (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P37455 Family Representative	single-stranded DNA binding GO:0003697	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnag_priming_activity	dnaG (Escherichia coli K-12) UniProtKB:P0ABS5 Family Representative	DNA-directed RNA polymerase activity GO:0003899	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnag_priming_activity	dnaG (Pseudomonas putida KT2440) UniProtKB:P0A118 Family Representative	DNA-directed RNA polymerase activity GO:0003899	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnag_priming_activity	dnaG (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P05096 Family Representative	DNA-directed RNA polymerase activity GO:0003899	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnaea_polymerase	dnaE (Escherichia coli K-12) UniProtKB:P10443 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).
dnaea_polymerase	dnaEA (Pseudomonas putida KT2440) UniProtKB:Q88MG5 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).
dnaq_proofreading	dnaQ (Escherichia coli K-12) UniProtKB:P03007 Family Representative	3'-5'-DNA exonuclease activity GO:0008296	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnaq_proofreading	dnaQ (Pseudomonas putida KT2440) UniProtKB:Q88FF6 Family Representative	3'-5'-DNA exonuclease activity GO:0008296	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnae_php_polymerase	dnaE1 (Mycobacterium tuberculosis H37Rv) UniProtKB:P9WNT7 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).
dnae_php_proofreading	dnaE1 (Mycobacterium tuberculosis H37Rv) UniProtKB:P9WNT7 Family Representative	DNA-specific proofreading exonuclease activity GO:0008296	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnae3_primer_extension	dnaE (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:O34623 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).
polc_polymerase	polC (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P13267 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).
polc_proofreading	polC (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P13267 Family Representative	DNA-specific proofreading exonuclease activity GO:0008296	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
clamp_loader_activity_complex	PROTEIN_COMPLEX Gene	DNA clamp loader activity GO:0003689	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
dnan_processivity_activity	dnaN (Escherichia coli K-12) UniProtKB:P0A988 Family Representative	DNA polymerase processivity factor activity GO:0030337	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnan_processivity_activity	dnaN (Pseudomonas putida KT2440) UniProtKB:P0A120 Family Representative	DNA polymerase processivity factor activity GO:0030337	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnan_processivity_activity	dnaN (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P05649 Family Representative	DNA polymerase processivity factor activity GO:0030337	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ecoli_primer_removal_activity	polA (Escherichia coli K-12) UniProtKB:P00582 Family Representative	5'-3' exonuclease activity GO:0008409	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bacillus_fena_removal_activity	fenA (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P54161 Family Representative	5'-flap endonuclease activity GO:0017108	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rnhc_hybrid_cleavage	rnhC (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:P94541 Family Representative	RNA-DNA hybrid ribonuclease activity GO:0004523	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pola_flap_processing	polA (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:O34996 Family Representative	5'-flap endonuclease activity GO:0017108	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ecoli_gap_filling_activity	polA (Escherichia coli K-12) UniProtKB:P00582 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).
bacillus_gap_filling_activity	polA (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:O34996 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).
ligation_activity	ligA (Escherichia coli K-12) UniProtKB:P15042 Family Representative	DNA ligase (NAD+) activity GO:0003911	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ligation_activity	ligA (Pseudomonas putida KT2440) UniProtKB:Q88F25 Family Representative	DNA ligase (NAD+) activity GO:0003911	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ligation_activity	ligA (Bacillus subtilis subsp. subtilis str. 168) UniProtKB:O31498 Family Representative	DNA ligase (NAD+) activity GO:0003911	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
torsional_stress_relief_complex	PROTEIN_COMPLEX Gene	DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity GO:0003918	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
myctu_gyrase_torsional_relief_complex	PROTEIN_COMPLEX Gene	DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity GO:0003918	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
daughter_dna_unlinking_complex	PROTEIN_COMPLEX Gene	DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity GO:0003918	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
myctu_gyrase_decatenation_complex	PROTEIN_COMPLEX Gene	DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity GO:0003918	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
holc_adaptor	holC (Escherichia coli K-12) UniProtKB:P28905 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).
holc_adaptor	holC (Pseudomonas putida KT2440) UniProtKB:Q88P74 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).
tau_coupling_activity	dnaX (Escherichia coli K-12) UniProtKB:P06710 Family Representative	protein complex scaffold activity GO:0140378	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dnaa_origin_initiation_activity	DnaA origin initiators PANTHER:PTHR30050:SF2 Family	DNA replication origin binding GO:0003688	Family Review Missing No supported structured family review is available for PANTHER:PTHR30050:SF2.
dnac_helicase_loading_activity	DnaC helicase loaders PANTHER:PTHR30050:SF9 Family	replicative DNA helicase loader activity No function ID	No Function Id The family function has no GO identifier for comparison; prose is not matched.
dnad_origin_recruitment	DnaD initiation factors PANTHER:PTHR37293:SF6 Family	DNA replication origin binding GO:0003688	Family Review Missing No supported structured family review is available for PANTHER:PTHR37293:SF6.
dnab_loading_accessory	Bacillus DnaB initiation accessory family Family	DNA binding GO:0003677	Family Id Missing The family has no identifier linking it to a curated family review.
dnai_loader	DnaI helicase loaders PANTHER:PTHR30050:SF8 Family	ATP hydrolysis activity GO:0016887	Family Review Missing No supported structured family review is available for PANTHER:PTHR30050:SF8.
dcia_helicase_loading_activity	DciA helicase-loading family Pfam:PF05258 Family	replicative DNA helicase loader activity No function ID	No Function Id The family function has no GO identifier for comparison; prose is not matched.
dnab_helicase	DnaB-family replicative helicases; Bacillus protein named DnaC PANTHER:PTHR30153:SF2 Family	5'-3' DNA helicase activity GO:0043139	Family Review Missing No supported structured family review is available for PANTHER:PTHR30153:SF2.
ssb_template_protection	Bacterial SSB family PANTHER:PTHR10302:SF27 Family	single-stranded DNA binding GO:0003697	Family Review Missing No supported structured family review is available for PANTHER:PTHR10302:SF27.
dnag_priming_activity	DnaG RNA primases PANTHER:PTHR30313:SF2 Family	DNA-directed RNA polymerase activity GO:0003899	Family Review Missing No supported structured family review is available for PANTHER:PTHR30313:SF2.
dnaea_polymerase	Replicative DnaE1 proteins with separate DnaQ proofreading PANTHER:PTHR32294:SF0 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.
dnaq_proofreading	DnaQ epsilon proofreading subunits PANTHER:PTHR30231:SF41 Family	3'-5'-DNA exonuclease activity GO:0008296	Family Review Missing No supported structured family review is available for PANTHER:PTHR30231:SF41.
dnae_php_polymerase	DnaE1 proteins with experimentally active intrinsic PHP proofreader PANTHER:PTHR32294:SF0 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.
dnae_php_proofreading	DnaE1 proteins with experimentally active intrinsic PHP proofreader PANTHER:PTHR32294:SF0 Family	DNA-specific proofreading exonuclease activity GO:0008296	Family Function Unreviewed Family review leaves GO:0008408 UNRESOLVED. Intrinsic exonuclease activity is not a blanket SF0 property. M. tuberculosis P9WNT7 has directly measured PHP exonuclease activity, whereas E. coli/Pseudomonas alpha implementations rely on separate DnaQ and Bacillus DnaE3 errors can be proofread by PolC. PolC provides a separate intrinsic proofreading domain. The comparative survey finds variable PHP inactivation across all four C-family groups. Retain experimentally supported P9WNT7 and PolC activity, and target-specific negative/uncertain DnaE2 judgments, without a whole-SF0 grant or denial. A general transfer rule remains unresolved until finer clades or a curated residue model have been established; a domain name is insufficient.
dnae3_primer_extension	Bacillus DnaE3 primer-extension implementation PANTHER:PTHR32294:SF0 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.
polc_polymerase	PolC polymerase and fused proofreading nuclease PANTHER:PTHR32294:SF5 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.
polc_proofreading	PolC polymerase and fused proofreading nuclease PANTHER:PTHR32294:SF5 Family	DNA-specific proofreading exonuclease activity GO:0008296	Family Function Unreviewed Family review leaves GO:0008408 UNRESOLVED. Intrinsic exonuclease activity is not a blanket SF0 property. M. tuberculosis P9WNT7 has directly measured PHP exonuclease activity, whereas E. coli/Pseudomonas alpha implementations rely on separate DnaQ and Bacillus DnaE3 errors can be proofread by PolC. PolC provides a separate intrinsic proofreading domain. The comparative survey finds variable PHP inactivation across all four C-family groups. Retain experimentally supported P9WNT7 and PolC activity, and target-specific negative/uncertain DnaE2 judgments, without a whole-SF0 grant or denial. A general transfer rule remains unresolved until finer clades or a curated residue model have been established; a domain name is insufficient.
dnan_processivity_activity	DnaN beta sliding clamps PANTHER:PTHR30478:SF0 Family	DNA polymerase processivity factor activity GO:0030337	Family Review Missing No supported structured family review is available for PANTHER:PTHR30478:SF0.
ecoli_primer_removal_activity	E. coli Pol I primer replacement implementation PANTHER:PTHR10133:SF27 Family	5'-3' exonuclease activity GO:0008409	Family Function Unreviewed Family review leaves GO:0008409 UNRESOLVED. The 5' nuclease domain is a bacterial Pol I feature (present in E. coli and P. putida PolA) and is absent from T7-type, Pol nu and Pol theta members, all of which share SF27 or SF62 with Pol I-type proteins, so no PANTHER family or subfamily id captures it. Ground it per protein or by the 5' nuclease domain signature instead.
bacillus_fena_removal_activity	FenA discrete flap nucleases PANTHER:PTHR42646:SF2 Family	5'-flap endonuclease activity GO:0017108	Family Review Missing No supported structured family review is available for PANTHER:PTHR42646:SF2.
rnhc_hybrid_cleavage	RNase HIII proteins (InterPro IPR004641) PANTHER:PTHR10954:SF23 Family	RNA-DNA hybrid ribonuclease activity GO:0004523	Family Review Missing No supported structured family review is available for PANTHER:PTHR10954:SF23.
pola_flap_processing	Bacillus PolA polymerase and flap nuclease PANTHER:PTHR10133:SF27 Family	5'-flap endonuclease activity GO:0017108	Family Function Unreviewed The family review has no applicable adjudication supporting or excluding GO:0017108.
ecoli_gap_filling_activity	E. coli Pol I primer replacement implementation PANTHER:PTHR10133:SF27 Family	DNA-directed DNA polymerase activity GO:0003887	Family Supported Family review supports GO:0003887 FAMILY_WIDE. Holds for every subfamily with characterized members: SF27 (E. coli Pol I; human Pol nu; P. putida PolA conserves all checked polymerase active-site residues), SF62 (human Pol theta), and the plant organellar polymerases, which PAINT covers through the root IBD. This covers the family-level PANTHER:PTHR10133 grounding of the PolA annoton in the nucleotide excision repair module. Exonuclease-deficient members (Thermus Pol I) retain polymerase activity.
bacillus_gap_filling_activity	Bacillus PolA polymerase and flap nuclease PANTHER:PTHR10133:SF27 Family	DNA-directed DNA polymerase activity GO:0003887	Family Supported Family review supports GO:0003887 FAMILY_WIDE. Holds for every subfamily with characterized members: SF27 (E. coli Pol I; human Pol nu; P. putida PolA conserves all checked polymerase active-site residues), SF62 (human Pol theta), and the plant organellar polymerases, which PAINT covers through the root IBD. This covers the family-level PANTHER:PTHR10133 grounding of the PolA annoton in the nucleotide excision repair module. Exonuclease-deficient members (Thermus Pol I) retain polymerase activity.
ligation_activity	NAD-dependent LigA ligases PANTHER:PTHR23389:SF9 Family	DNA ligase (NAD+) activity GO:0003911	Family Supported Family review supports GO:0003911 for PANTHER:PTHR23389:SF9. The bacterial nucleotide-excision repair module asserts this activity for its LigA step, grounded to PTHR23389:SF9. Every one of the 762 reviewed SF9 members is a DNA ligase (LigA, LigA1/LigA2 paralogs, or archaeal LigN), and PAINT places the activity on the bacterial LigA node. The activity is false for the eukaryotic clamp-loader/unloader subfamilies (SF6, SF3, SF21, SF11), which are AAA+ PCNA-loading or unloading subunits.
holc_adaptor	HolC chi accessory adaptors PANTHER:PTHR38767:SF1 Family	protein-macromolecule adaptor activity GO:0030674	Family Review Missing No supported structured family review is available for PANTHER:PTHR38767:SF1.
tau_coupling_activity	Full-length tau scaffolding form of DnaX PANTHER:PTHR11669:SF0 Family	protein complex scaffold activity GO:0140378	Family Function Unreviewed The family review has no applicable adjudication supporting or excluding GO:0140378.

Gene-review completeness (52/52 grounded genes reviewed)

35 complete review(s) · 0 with deep research · 0 missing review · 52 reviewed but lacking deep research

Gene	Review	Complete	Deep research
dciA Q9KPH3	✓	1/2	✗
dnaA P03004	✓	✓	✗
dnaA P05648	✓	23/24	✗
dnaA P0A116	✓	9/10	✗
dnaB P07908	✓	✓	✗
dnaB P0ACB0	✓	✓	✗
dnaB Q88DF2	✓	✓	✗
dnaC P0AEF0	✓	24/25	✗
dnaC P37469	✓	✓	✗
dnaD P39787	✓	✓	✗
dnaE O34623	✓	✓	✗
dnaE P10443	✓	✓	✗
dnaE1 P9WNT7	✓	9/10	✗
dnaEA Q88MG5	✓	7/8	✗
dnaG P05096	✓	✓	✗
dnaG P0A118	✓	✓	✗
dnaG P0ABS5	✓	✓	✗
dnaI P06567	✓	7/8	✗
dnaN P05649	✓	✓	✗
dnaN P0A120	✓	✓	✗
dnaN P0A988	✓	60/61	✗
dnaQ P03007	✓	✓	✗
dnaQ Q88FF6	✓	✓	✗
dnaX P06710	✓	✓	✗
dnaX P09122	✓	✓	✗
dnaX Q88F30	✓	✓	✗
fenA P54161	✓	✓	✗
gyrA P0AES4	✓	42/43	✗
gyrA P9WG47	✓	20/26	✗
gyrB P0AES6	✓	✓	✗
gyrB P9WG45	✓	19/20	✗
holA P28630	✓	✓	✗
holA P54459	✓	7/8	✗
holA Q88DM9	✓	✓	✗
holB P28631	✓	41/42	✗
holB P37540	✓	8/9	✗
holB Q88LG7	✓	8/9	✗
holC P28905	✓	38/40	✗
holC Q88P74	✓	✓	✗
holD Q88Q02	✓	✓	✗
ligA O31498	✓	✓	✗
ligA P15042	✓	✓	✗
ligA Q88F25	✓	✓	✗
parC P0AFI2	✓	✓	✗
parE P20083	✓	✓	✗
polA O34996	✓	11/12	✗
polA P00582	✓	✓	✗
polC P13267	✓	✓	✗
rnhC P94541	✓	✓	✗
ssb P0AGE0	✓	✓	✗
ssb Q88QK5	✓	✓	✗
ssbA P37455	✓	✓	✗

Tree

Bacterial chromosomal DNA replicationBiological Processbacterial_chromosomal_dna_replication

Parts
1. 1. DnaA origin recognition and opening
2. DnaA origin recognition and openingMolecular Functiondnaa_origin_initiation
  
  Annotons
  - DnaA origin recognition and opening Family: DnaA origin initiators
3. 2. Replicative helicase loading
4. Replicative helicase loadingBiological Processreplicative_helicase_loading
  
  Variants
  1. Replicative helicase loading implementations by lineage-specific loading architecture [Route] (One Or More)
    
    DnaC-dependent helicase loadingMolecular Functiondnac_helicase_loading
    
    Annotons
    
    DnaC-dependent helicase loading Family: DnaC helicase loaders
    
    Bacillus DnaD-DnaB-DnaI loading routeBiological Processbacillus_helicase_loading
    
    Annotons
    
    DnaD origin recognition Family: DnaD initiation factors
    
    Bacillus DnaB DNA-binding loading accessory Family: Bacillus DnaB initiation accessory family
    
    DnaI helicase loader ATPase Family: DnaI helicase loaders
    
    DciA-dependent helicase loadingMolecular Functiondcia_helicase_loading
    
    Annotons
    
    DciA-dependent helicase loading Family: DciA helicase-loading family
5. 3. Fork unwinding and single-strand protection
6. Fork unwinding and single-strand protectionBiological Processfork_unwinding_protection
  
  Annotons
  - Replicative DnaB-family helicase Family: DnaB-family replicative helicases; Bacillus protein named DnaC
  - SSB single-strand protection Family: Bacterial SSB family
7. 4. DnaG RNA primer synthesis
8. DnaG RNA primer synthesisMolecular Functiondnag_priming
  
  Annotons
  - DnaG RNA primer synthesis Family: DnaG RNA primases
9. 5. Replicative synthesis and proofreading
10. Replicative synthesis and proofreadingBiological Processreplicative_synthesis_proofreading
  
  Variants
  1. Replicative synthesis and proofreading implementations by replicative polymerase and proofreading architecture [Route] (One Or More)
    
    DnaE1 with separate DnaQ proofreadingBiological Processdnae_dnaq_synthesis
    
    Annotons
    
    Replicative DnaE1 synthesis Family: Replicative DnaE1 proteins with separate DnaQ proofreading
    
    DnaQ proofreading contribution Family: DnaQ epsilon proofreading subunits
    
    DnaE1 with active intrinsic PHP proofreadingBiological Processdnae_php_synthesis
    
    Annotons
    
    DnaE1 polymerase activity Family: DnaE1 proteins with experimentally active intrinsic PHP proofreader
    
    Active PHP proofreading Family: DnaE1 proteins with experimentally active intrinsic PHP proofreader
    
    PolC-DnaE3 polymerase handoffBiological Processpolc_dnae3_synthesis
    
    Annotons
    
    DnaE3 RNA-primer extension Family: Bacillus DnaE3 primer-extension implementation
    
    PolC bulk replicative synthesis Family: PolC polymerase and fused proofreading nuclease
    
    PolC fused proofreading activity Family: PolC polymerase and fused proofreading nuclease
11. 6. DnaX-HolA-HolB clamp loader
12. DnaX-HolA-HolB clamp loaderProtein Complexclamp_loader_activity
  
  Annotons
  - DnaX-HolA-HolB clamp loader Protein Complex: DnaX-HolA-HolB clamp loader
13. 7. DnaN sliding-clamp processivity
14. DnaN sliding-clamp processivityMolecular Functiondnan_processivity
  
  Annotons
  - DnaN sliding-clamp processivity Family: DnaN beta sliding clamps
15. 8. RNA-primer removal
16. RNA-primer removalBiological Processrna_primer_removal
  
  Variants
  1. RNA-primer removal implementations by primer-processing enzyme architecture [Route] (One Or More)
    
    PolA RNA-primer removalMolecular Functionecoli_primer_removal
    
    Annotons
    
    PolA RNA-primer removal Family: E. coli Pol I primer replacement implementation
    
    FenA primer-flap removalMolecular Functionbacillus_fena_removal
    
    Annotons
    
    FenA primer-flap removal Family: FenA discrete flap nucleases
    
    RNase HIII-PolA primer processingBiological Processbacillus_rnhc_pola_removal
    
    Annotons
    
    RNase HIII hybrid cleavage Family: RNase HIII proteins (InterPro IPR004641)
    
    PolA flap processing Family: Bacillus PolA polymerase and flap nuclease
17. 9. DNA gap filling after primer removal
18. DNA gap filling after primer removalBiological Processdna_gap_filling
  
  Variants
  1. DNA gap filling after primer removal implementations by experimentally grounded polymerase capacity with physiological-role caveats [Route] (One Or More)
    
    PolA DNA gap fillingMolecular Functionecoli_gap_filling
    
    Annotons
    
    PolA DNA gap filling Family: E. coli Pol I primer replacement implementation
    
    Bacillus PolA gap-filling capacityMolecular Functionbacillus_gap_filling
    
    Annotons
    
    Bacillus PolA gap-filling capacity Family: Bacillus PolA polymerase and flap nuclease
19. 10. LigA nick sealing
20. LigA nick sealingMolecular Functionligation
  
  Annotons
  - LigA nick sealing Family: NAD-dependent LigA ligases
21. 11. Torsional-stress relief during fork progression
22. Torsional-stress relief during fork progressionBiological Processtorsional_stress_relief
  
  Variants
  1. Torsional-stress relief during fork progression implementations by demonstrated supercoiling-relief implementation [Realizer] (One Or More)
    
    GyrAB torsional-stress reliefProtein Complexecoli_gyrab_torsional_relief
    
    Annotons
    
    GyrAB torsional-stress relief Protein Complex: GyrAB torsional-stress relief
    
    H37Rv GyrAB supercoiling implementationProtein Complexmyctu_gyrase_torsional_relief
    
    Annotons
    
    H37Rv GyrAB supercoiling implementation Protein Complex: Mycobacterium tuberculosis H37Rv DNA gyrase A2B2 complex
23. 12. Daughter-DNA unlinking
24. Daughter-DNA unlinkingBiological Processdaughter_dna_unlinking
  
  Variants
  1. Daughter-DNA unlinking implementations by demonstrated decatenation implementation [Realizer] (One Or More)
    
    ParCE daughter-DNA unlinkingProtein Complexecoli_parce_decatenation
    
    Annotons
    
    ParCE daughter-DNA unlinking Protein Complex: ParCE daughter-DNA unlinking
    
    H37Rv GyrAB decatenation implementationProtein Complexmyctu_gyrase_decatenation
    
    Annotons
    
    H37Rv GyrAB decatenation implementation Protein Complex: Mycobacterium tuberculosis H37Rv DNA gyrase A2B2 complex
25. HolC-HolD clamp-loader accessory context optional
26. HolC-HolD clamp-loader accessory contextBiological Processholc_hold_accessory
  
  Annotons
  - HolC accessory adaptor Family: HolC chi accessory adaptors
  - Pseudomonas HolD psi contribution Family: Divergent Pseudomonas HolD psi accessory family
27. Tau-specific replisome coupling optional
28. Tau-specific replisome couplingMolecular Functiontau_coupling
  
  Annotons
  - Tau-specific replisome coupling Family: Full-length tau scaffolding form of DnaX

Details

Context

BacteriaNCBITaxon:2

Bacterial chromosomal DNA replicationBiological Processbacterial_chromosomal_dna_replication

DNA replicationGO:0006260

Context

BacteriaNCBITaxon:2

Connections

dnaa_origin_initiation -> replicative_helicase_loading Provides Input For

Origin recognition precedes recruitment/loading.

PMID:19968790

Ordered association of helicase loader proteins with the Bacillus subtilis origin of replication in vivo.

Bacillus origin recruitment proceeds through ordered DnaA, DnaD and DnaB association followed by DnaI-mediated helicase loading.

We found that there was a clear order of stable association with oriC; DnaA, DnaD, DnaB, and finally DnaI-mediated loading of helicase.

replicative_helicase_loading -> fork_unwinding_protection Provides Input For

Productive loading precedes processive unwinding.

PMID:42927770

Structural basis of DnaB ring opening by the ancestral helicase loader DciA.

Vibrio DciA promotes topological helicase loading; the intact protein is more effective than its isolated domains.

Under these conditions, full-length DciA supported efficient duplex unwinding, whereas the isolated C-terminal fragment was completely inactive

dnag_priming -> replicative_synthesis_proofreading Provides Input For

RNA primers supply extendable ends.

PMID:30945375

A structural view of bacterial DNA replication.

DnaG primase produces RNA primers while interacting with the replicative helicase.

DnaB binds the DnaG primase that synthesizes RNA primers on both strands.

PMID:20122408

Reconstitution of the B. subtilis replisome with 13 proteins including two distinct replicases.

PolC supports leading-strand synthesis in the reconstitution, while lagging-strand synthesis additionally requires DnaG and DnaE.

Leading strand synthesis requires PolC plus ten proteins; lagging strand synthesis additionally requires primase and DnaE.

clamp_loader_activity -> dnan_processivity Provides Input For

Clamp loading supplies processivity factors on DNA.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

The Bacillus DnaX/HolA/HolB complex loads DnaN clamps in an ATP-dependent reaction.

The CLC additionally interacts with and loads two ring-shaped DnaN sliding-clamps onto each complementary strand at oriC in an ATP-dependent manner

rna_primer_removal -> dna_gap_filling Provides Input For

Primer removal creates substrates for DNA replacement.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

Okazaki-fragment maturation requires RNA-primer removal before the fragments form a continuous DNA strand.

Okazaki fragment maturation involves highly coordinated reactions that remove RNA primers and convert the discrete fragments into a continuous lagging strand.

PMID:6262323

Replication of phi X174 dna with purified enzymes. I. Conversion of viral DNA to a supercoiled, biologically active duplex.

E. coli Pol I fills a residual gap and replaces the RNA primer with DNA in a purified synthesis system.

E. coli DNA polymerase I was needed to fill the short gap left by DNA polymerase III holoenzyme, and to remove the primer and replace it with DNA.

dna_gap_filling -> ligation Provides Input For

Mature DNA gaps must be filled before nick sealing.

PMID:6262323

Replication of phi X174 dna with purified enzymes. I. Conversion of viral DNA to a supercoiled, biologically active duplex.

Ligase and gyrase are needed after PolI-mediated primer replacement to obtain the completed supercoiled viral duplex.

Production of supercoiled RF required the further actions of E. coli DNA ligase and gyrase.

Part 1: DnaA origin recognition and opening

DnaA origin recognition and openingMolecular Functiondnaa_origin_initiation

Annotons

DnaA origin recognition and opening

dnaa_origin_initiation_activity

Participant: Family: DnaA origin initiators

Family:

DnaA origin initiatorsPANTHER:PTHR30050:SF2

Representative Members: dnaA (Escherichia coli K-12)UniProtKB:P03004 dnaA (Pseudomonas putida KT2440)UniProtKB:P0A116 dnaA (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P05648

Function

DNA replication origin bindingGO:0003688

ATP-bound DnaA recognizes oriC and promotes local opening with lineage-specific partners; origin binding alone is not a complete initiation apparatus.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

ATP-bound DnaA promotes origin strand opening with nucleoid-associated factors in the two model bacteria.

together with nucleoid-associated proteins, recognizes and “melts” parental DNA strands at oriC to initiate DNA replication

Part 2: Replicative helicase loading

Replicative helicase loadingBiological Processreplicative_helicase_loading

PMID:36877032

Diverse Mechanisms of Helicase Loading during DNA Replication Initiation in Bacteria.

A non-ATPase DciA implementation provides an alternative to DnaC/DnaI-type loading.

DciA is not an ATPase, and yet it serves as a helicase operator, providing a function analogous to that of DnaC and DnaI across diverse bacterial species.

Variant set: Replicative helicase loading implementations by lineage-specific loading architecture [Route] (One Or More)

DnaC-dependent helicase loadingMolecular Functiondnac_helicase_loading

Annotons

DnaC-dependent helicase loading

dnac_helicase_loading_activity

Participant: Family: DnaC helicase loaders

Family:

DnaC helicase loadersPANTHER:PTHR30050:SF9

Representative Members: dnaC (Escherichia coli K-12)UniProtKB:P0AEF0

Function

replicative DNA helicase loader activity

Loads and remodels DnaB rings. The gene review proposes the loader activity because no exact GO activity is asserted.

PMID:23562643

The bacterial DnaC helicase loader is a DnaB ring breaker.

E. coli DnaC opens the DnaB ring and can load it onto DNA.

the DnaC isolated helicase-binding domain can both load DnaB onto DNA and increase the efficiency by which the helicase acts on substrates in vitro.

PMID:30797687

Physical Basis for the Loading of a Bacterial Replicative Helicase onto DNA.

DnaC ATP hydrolysis after DNA binding permits closure of the helicase into a primase-compatible state.

Upon binding DNA, DnaC hydrolyzes ATP, allowing DnaB to isomerize into a topologically closed, pre-translocation state competent to bind primase.

Bacillus DnaD-DnaB-DnaI loading routeBiological Processbacillus_helicase_loading

DnaA precedes DnaD, DnaB and DnaI-dependent recruitment. The Bacillus helicase is named DnaC. Do not equate a restart-substrate reconstitution with oriC initiation.

Annotons

DnaD origin recognition

dnad_origin_recruitment

Participant: Family: DnaD initiation factors

Family:

DnaD initiation factorsPANTHER:PTHR37293:SF6

Representative Members: dnaD (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P39787

Function

DNA replication origin bindingGO:0003688

Recognizes an oriC single-stranded element during recruitment.

PMID:37093985

The DNA replication initiation protein DnaD recognises a specific strand of the Bacillus subtilis chromosome origin.

DnaD recognizes an oriC single-stranded element as part of the Bacillus loading architecture.

Biochemical and genetic data support the model that DnaD recognizes a new single-stranded DNA (ssDNA) motif located in oriC, the DnaD Recognition Element (DRE).

PMID:19968790

Ordered association of helicase loader proteins with the Bacillus subtilis origin of replication in vivo.

Bacillus origin recruitment proceeds through ordered DnaA, DnaD and DnaB association followed by DnaI-mediated helicase loading.

We found that there was a clear order of stable association with oriC; DnaA, DnaD, DnaB, and finally DnaI-mediated loading of helicase.

Bacillus DnaB DNA-binding loading accessory

dnab_loading_accessory

Participant: Family: Bacillus DnaB initiation accessory family

Family:

Bacillus DnaB initiation accessory family

Representative Members: dnaB (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P07908

Function

DNA bindingGO:0003677

Cooperates with DnaI in functional delivery of DnaC; not the DnaB helicase of E. coli.

PMID:12718886

A two-protein strategy for the functional loading of a cellular replicative DNA helicase.

Bacillus DnaI and DnaB cooperate in functional delivery of the DnaC helicase onto DNA.

We show that DnaI and DnaB interact physically and functionally with the DnaC helicase and mediate its functional delivery onto DNA.

PMID:19968790

Ordered association of helicase loader proteins with the Bacillus subtilis origin of replication in vivo.

Bacillus origin recruitment proceeds through ordered DnaA, DnaD and DnaB association followed by DnaI-mediated helicase loading.

We found that there was a clear order of stable association with oriC; DnaA, DnaD, DnaB, and finally DnaI-mediated loading of helicase.

DnaI helicase loader ATPase

dnai_loader

Participant: Family: DnaI helicase loaders

Family:

DnaI helicase loadersPANTHER:PTHR30050:SF8

Representative Members: dnaI (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P06567

Function

ATP hydrolysis activityGO:0016887

ATPase activity participates in functional helicase loading; the family and native-origin recruitment role are required in addition to ATP hydrolysis.

PMID:12718886

A two-protein strategy for the functional loading of a cellular replicative DNA helicase.

Bacillus DnaI and DnaB cooperate in functional delivery of the DnaC helicase onto DNA.

We show that DnaI and DnaB interact physically and functionally with the DnaC helicase and mediate its functional delivery onto DNA.

PMID:19968790

Ordered association of helicase loader proteins with the Bacillus subtilis origin of replication in vivo.

Bacillus origin recruitment proceeds through ordered DnaA, DnaD and DnaB association followed by DnaI-mediated helicase loading.

We found that there was a clear order of stable association with oriC; DnaA, DnaD, DnaB, and finally DnaI-mediated loading of helicase.

PMID:17003052

Helicase binding to DnaI exposes a cryptic DNA-binding site during helicase loading in Bacillus subtilis.

DnaI directly binds and hydrolyzes ATP; this chemistry is distinct from the complete cooperative loading reaction.

DnaI binds ATP and exhibits ATPase activity that is not stimulated by ssDNA

DciA-dependent helicase loadingMolecular Functiondcia_helicase_loading

The 2016 PAO1 native genetics supports a DciA-dependent route but is not an exact Q9KPH3 assay. No verified KT2440 DciA representative is asserted.

Annotons

DciA-dependent helicase loading

dcia_helicase_loading_activity

Participant: Family: DciA helicase-loading family

Family:

DciA helicase-loading familyPfam:PF05258

Representative Members: dciA (Vibrio cholerae O1 biovar El Tor str. N16961)UniProtKB:Q9KPH3

Function

replicative DNA helicase loader activity

Vibrio Q9KPH3 matches the assayed 157-residue protein and deposited 9TZF entity2. Loading is tested on a fork with a streptavidin-blocked 5-prime ssDNA end; not a covalently closed circle.

PMID:42927770

Structural basis of DnaB ring opening by the ancestral helicase loader DciA.

Vibrio DciA promotes topological helicase loading; the intact protein is more effective than its isolated domains.

Under these conditions, full-length DciA supported efficient duplex unwinding, whereas the isolated C-terminal fragment was completely inactive

PMID:42927770

Structural basis of DnaB ring opening by the ancestral helicase loader DciA.

DciA stabilizes an open DnaB hexamer, providing a structural mechanism for DNA loading.

A 3.5 Å cryo-EM structure reveals a DnaB6·DciA3 complex in which DciA binds the periphery of the helicase and stabilizes a right-handed open-helical conformation with a single cracked interface.

PMID:27830752

DciA is an ancestral replicative helicase operator essential for bacterial replication initiation.

P. aeruginosa DciA is implicated in replicative-helicase operation during initiation.

We validate this hypothesis by establishing in Pseudomonas aeruginosa that DciA possesses the attributes of the replicative helicase-operating proteins associated with replication initiation.

Part 3: Fork unwinding and single-strand protection

Fork unwinding and single-strand protectionBiological Processfork_unwinding_protection

Annotons

Replicative DnaB-family helicase

dnab_helicase

Participant: Family: DnaB-family replicative helicases; Bacillus protein named DnaC

Family:

DnaB-family replicative helicases; Bacillus protein named DnaCPANTHER:PTHR30153:SF2

Representative Members: dnaB (Escherichia coli K-12)UniProtKB:P0ACB0 dnaB (Pseudomonas putida KT2440)UniProtKB:Q88DF2 dnaC (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P37469

Function

5'-3' DNA helicase activityGO:0043139

Unwinds parental duplex after loading.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

The Bacillus DnaC helicase encircles single-stranded DNA and unwinds the fork with 5-prime to 3-prime polarity.

Once released from DnaI, DnaC encircles ssDNA and unwinds forked DNA with 5'→3' polarity

SSB single-strand protection

ssb_template_protection

Participant: Family: Bacterial SSB family

Family:

Bacterial SSB familyPANTHER:PTHR10302:SF27

Representative Members: ssb (Escherichia coli K-12)UniProtKB:P0AGE0 ssb (Pseudomonas putida KT2440)UniProtKB:Q88QK5 ssbA (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P37455

Function

single-stranded DNA bindingGO:0003697

Protects exposed single-stranded DNA and supports replisome partners.

PMID:21955458

Characterization of the χψ subcomplex of Pseudomonas aeruginosa DNA polymerase III.

SSB protects exposed single-stranded DNA during replication and links it to the clamp-loader accessory complex.

During replication, single-stranded DNA-binding protein (SSB) coats and protects single-stranded DNA (ssDNA) and also interacts with the χψ heterodimer

Part 4: DnaG RNA primer synthesis

DnaG RNA primer synthesisMolecular Functiondnag_priming

Annotons

DnaG RNA primer synthesis

dnag_priming_activity

Participant: Family: DnaG RNA primases

Family:

DnaG RNA primasesPANTHER:PTHR30313:SF2

Representative Members: dnaG (Escherichia coli K-12)UniProtKB:P0ABS5 dnaG (Pseudomonas putida KT2440)UniProtKB:P0A118 dnaG (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P05096

Function

DNA-directed RNA polymerase activityGO:0003899

Makes RNA primers. Bacillus DnaE extension is separately represented in its dual-polymerase route.

PMID:30945375

A structural view of bacterial DNA replication.

DnaG primase produces RNA primers while interacting with the replicative helicase.

DnaB binds the DnaG primase that synthesizes RNA primers on both strands.

Part 5: Replicative synthesis and proofreading

Replicative synthesis and proofreadingBiological Processreplicative_synthesis_proofreading

PMID:41728957

Diversity and distribution of bacterial DNA polymerases.

Three major replicative catalytic-subunit configurations are DnaE1 alone, PolC with DnaE1, and PolC with DnaE3.

(i) DnaE1-only, (ii) PolC + DnaE1, and (iii) PolC + DnaE3

PMID:41728957

Diversity and distribution of bacterial DNA polymerases.

DnaE1 and PolC family membership does not ensure an active PHP proofreader.

Different fractions of inactivated PHP proofreaders are present in all four major C-family groups (DnaE1–3 and PolC).

PMID:41728957

Diversity and distribution of bacterial DNA polymerases.

DnaE2 is an error-prone accessory polymerase rather than a substitute for the ordinary replicative catalytic subunit.

DnaE2 polymerases, with few exceptions, have inactivated PHP domains, as they represent non-essential SOS-inducible TLS polymerases

Variant set: Replicative synthesis and proofreading implementations by replicative polymerase and proofreading architecture [Route] (One Or More)

DnaE1 with separate DnaQ proofreadingBiological Processdnae_dnaq_synthesis

Annotons

Replicative DnaE1 synthesis

dnaea_polymerase

Participant: Family: Replicative DnaE1 proteins with separate DnaQ proofreading

Family:

Replicative DnaE1 proteins with separate DnaQ proofreadingPANTHER:PTHR32294:SF0

Representative Members: dnaE (Escherichia coli K-12)UniProtKB:P10443 dnaEA (Pseudomonas putida KT2440)UniProtKB:Q88MG5

Function

DNA-directed DNA polymerase activityGO:0003887

Replicative DnaE1 extends DNA primers; DnaE2 repair enzymes are excluded despite broad family membership.

PMID:15611049

Reconstitution of a minimal DNA replicase from Pseudomonas aeruginosa and stimulation by non-cognate auxiliary factors.

A Pseudomonas minimal replicase supports efficient primer elongation with alpha-epsilon, beta clamp and tau3-delta-delta-prime.

Efficient primer elongation requires the presence of alphaepsilon, beta, and tau(3)deltadelta'.

PMID:41728957

Diversity and distribution of bacterial DNA polymerases.

Three major replicative catalytic-subunit configurations are DnaE1 alone, PolC with DnaE1, and PolC with DnaE3.

(i) DnaE1-only, (ii) PolC + DnaE1, and (iii) PolC + DnaE3

DnaQ proofreading contribution

dnaq_proofreading

Participant: Family: DnaQ epsilon proofreading subunits

Family:

DnaQ epsilon proofreading subunitsPANTHER:PTHR30231:SF41

Representative Members: dnaQ (Escherichia coli K-12)UniProtKB:P03007 dnaQ (Pseudomonas putida KT2440)UniProtKB:Q88FF6

Function

3'-5'-DNA exonuclease activityGO:0008296

Removes mismatched primer-terminal nucleotides in the alpha-epsilon implementation.

PMID:22206257

Architecture and conservation of the bacterial DNA replication machinery, an underexploited drug target.

The alpha polymerase is partnered with a distinct epsilon exonuclease that removes misincorporated primer-terminal nucleotides.

Each polymerase α subunit is accompanied by a proofreading ε subunit, an exonuclease that removes errantly incorporated nucleotides at the 3’ end of the newly synthesized strand.

DnaE1 with active intrinsic PHP proofreadingBiological Processdnae_php_synthesis

Annotons

DnaE1 polymerase activity

dnae_php_polymerase

Participant: Family: DnaE1 proteins with experimentally active intrinsic PHP proofreader

Family:

DnaE1 proteins with experimentally active intrinsic PHP proofreaderPANTHER:PTHR32294:SF0

Representative Members: dnaE1 (Mycobacterium tuberculosis H37Rv)UniProtKB:P9WNT7

Function

DNA-directed DNA polymerase activityGO:0003887

H37Rv DnaE1 is the polymerase construct expressed in M. smegmatis.

PMID:25894501

DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader.

Wild-type and PHP-mutant M. tuberculosis DnaE1 both retain directly measured DNA polymerase activity.

we found that wild-type and PHP mutant DnaE1MTB proteins also showed robust DNA polymerase activity

Active PHP proofreading

dnae_php_proofreading

Participant: Family: DnaE1 proteins with experimentally active intrinsic PHP proofreader

Family:

DnaE1 proteins with experimentally active intrinsic PHP proofreaderPANTHER:PTHR32294:SF0

Representative Members: dnaE1 (Mycobacterium tuberculosis H37Rv)UniProtKB:P9WNT7

Function

DNA-specific proofreading exonuclease activityGO:0008296

Requires measured proofreading activity; the presence of a PHP domain alone is insufficient. Additional mycobacterial proofreaders are not excluded.

PMID:25894501

DNA replication fidelity in Mycobacterium tuberculosis is mediated by an ancestral prokaryotic proofreader.

The intrinsic DnaE1 exonuclease can correct a terminal mismatch before DNA extension.

These data demonstrate that DnaE1MTB encodes an intrinsic 3′-5′ exonuclease activity that, at least in vitro, is capable of correcting mismatches.

PMID:39141351

An additional proofreader contributes to DNA replication fidelity in mycobacteria.

Noncanonical mycobacterial DnaQ provides additional proofreading alongside PHP.

mycobacterial DnaQ binds to the β clamp and functions synergistically with the PHP domain proofreader to correct replication errors.

PolC-DnaE3 polymerase handoffBiological Processpolc_dnae3_synthesis

The purified 2010 system uses a PriA restart/flapped minicircle, not oriC initiation. PolC/DnaE1 combinations in other clades are distinct from this Bacillus DnaE3 implementation.

Annotons

DnaE3 RNA-primer extension

dnae3_primer_extension

Participant: Family: Bacillus DnaE3 primer-extension implementation

Family:

Bacillus DnaE3 primer-extension implementationPANTHER:PTHR32294:SF0

Representative Members: dnaE (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:O34623

Function

DNA-directed DNA polymerase activityGO:0003887

Extends RNA primers before handoff; not a standalone replacement for PolC.

PMID:20122408

Reconstitution of the B. subtilis replisome with 13 proteins including two distinct replicases.

Both PolC and DnaE are required for the purified Bacillus fork system; DnaE extends RNA primers before transfer to PolC.

adding a stretch of deoxynucleotides to the RNA primer before handoff to PolC.

PMID:20122408

Reconstitution of the B. subtilis replisome with 13 proteins including two distinct replicases.

PolC supports leading-strand synthesis in the reconstitution, while lagging-strand synthesis additionally requires DnaG and DnaE.

Leading strand synthesis requires PolC plus ten proteins; lagging strand synthesis additionally requires primase and DnaE.

PolC bulk replicative synthesis

polc_polymerase

Participant: Family: PolC polymerase and fused proofreading nuclease

Family:

PolC polymerase and fused proofreading nucleasePANTHER:PTHR32294:SF5

Representative Members: polC (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P13267

Function

DNA-directed DNA polymerase activityGO:0003887

Carries the major synthesis role in the sampled Bacillus mechanism.

PMID:20122408

Reconstitution of the B. subtilis replisome with 13 proteins including two distinct replicases.

PolC is required for leading-strand synthesis in the purified Bacillus replisome; lagging-strand synthesis additionally requires DnaE.

Leading strand synthesis requires PolC plus ten proteins; lagging strand synthesis additionally requires primase and DnaE.

PolC fused proofreading activity

polc_proofreading

Participant: Family: PolC polymerase and fused proofreading nuclease

Family:

PolC polymerase and fused proofreading nucleasePANTHER:PTHR32294:SF5

Representative Members: polC (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P13267

Function

DNA-specific proofreading exonuclease activityGO:0008296

Provides its own 3-prime proofreading and can proofread errors made by DnaE.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

Bacillus PolC contains polymerase and proofreading exonuclease activities in one polypeptide.

PolC is a bifunctional enzyme that contains a 5'→ 3' polymerase domain and a DEDDh-family 3'→ 5' proofreading exonuclease domain within a single polypeptide

PMID:28878042

Interactions of the Bacillus subtilis DnaE polymerase with replisomal proteins modulate its activity and fidelity.

PolC exonuclease can correct errors introduced by DnaE in the biochemical complex.

its errors are proofread by the 3' > 5' exonuclease activity of PolC in a stable template-DnaE-PolC complex.

Part 6: DnaX-HolA-HolB clamp loader

DnaX-HolA-HolB clamp loaderProtein Complexclamp_loader_activity

Annotons

DnaX-HolA-HolB clamp loader

clamp_loader_activity_complex

Participant: Protein Complex: DnaX-HolA-HolB clamp loader

Protein Complex:

DnaX-HolA-HolB clamp loader

Active units:

DnaX tau/gamma subunits3 in sampled minimal loaders

Participant: Family: DnaX clamp-loader subunits

Family:

DnaX clamp-loader subunitsPANTHER:PTHR11669:SF0

Representative Members: dnaX (Escherichia coli K-12)UniProtKB:P06710 dnaX (Pseudomonas putida KT2440)UniProtKB:Q88F30 dnaX (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P09122

Role: Role-bearing component of the assembled DnaX-HolA-HolB clamp loader.

HolA delta1

Participant: Family: HolA delta clamp-loader subunits

Family:

HolA delta clamp-loader subunitsPANTHER:PTHR34388:SF1

Representative Members: holA (Escherichia coli K-12)UniProtKB:P28630 holA (Pseudomonas putida KT2440)UniProtKB:Q88DM9 holA (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P54459

Role: Role-bearing component of the assembled DnaX-HolA-HolB clamp loader.

HolB delta-prime1

Participant: Family: HolB delta-prime clamp-loader subunits

Family:

HolB delta-prime clamp-loader subunitsPANTHER:PTHR11669:SF8

Representative Members: holB (Escherichia coli K-12)UniProtKB:P28631 holB (Pseudomonas putida KT2440)UniProtKB:Q88LG7 holB (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P37540

Role: Role-bearing component of the assembled DnaX-HolA-HolB clamp loader.

Function

DNA clamp loader activityGO:0003689

The assembled complex loads clamps. No single ATPase or one partial subunit set supplies complete clamp-loader activity.

PMID:15611049

Reconstitution of a minimal DNA replicase from Pseudomonas aeruginosa and stimulation by non-cognate auxiliary factors.

A Pseudomonas minimal replicase supports efficient primer elongation with alpha-epsilon, beta clamp and tau3-delta-delta-prime.

Efficient primer elongation requires the presence of alphaepsilon, beta, and tau(3)deltadelta'.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

The Bacillus DnaX/HolA/HolB complex loads DnaN clamps in an ATP-dependent reaction.

The CLC additionally interacts with and loads two ring-shaped DnaN sliding-clamps onto each complementary strand at oriC in an ATP-dependent manner

PMID:23525462

Insights into the structure and assembly of the Bacillus subtilis clamp-loader complex and its interaction with the replicative helicase.

Mass spectrometry supports a heteropentameric Bacillus tau3-delta-delta-prime loader.

a hetero-pentameric τ3-δ-δ' Bacillus subtilis clamp-loader assembles via multiple pathways

Part 7: DnaN sliding-clamp processivity

DnaN sliding-clamp processivityMolecular Functiondnan_processivity

Annotons

DnaN sliding-clamp processivity

dnan_processivity_activity

Participant: Family: DnaN beta sliding clamps

Family:

DnaN beta sliding clampsPANTHER:PTHR30478:SF0

Representative Members: dnaN (Escherichia coli K-12)UniProtKB:P0A988 dnaN (Pseudomonas putida KT2440)UniProtKB:P0A120 dnaN (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P05649

Function

DNA polymerase processivity factor activityGO:0030337

The beta clamp supports sustained synthesis after loading; this role is distinct from DNA polymerase catalysis.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

DnaN binding increases polymerase processivity and synthesis rate.

DnaE/α interacts with DnaN/β via the CBM, increasing the processivity and rate of DNA synthesis by the Pol III HE

Part 8: RNA-primer removal

RNA-primer removalBiological Processrna_primer_removal

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

Okazaki-fragment maturation requires RNA-primer removal before the fragments form a continuous DNA strand.

Okazaki fragment maturation involves highly coordinated reactions that remove RNA primers and convert the discrete fragments into a continuous lagging strand.

Variant set: RNA-primer removal implementations by primer-processing enzyme architecture [Route] (One Or More)

PolA RNA-primer removalMolecular Functionecoli_primer_removal

Annotons

PolA RNA-primer removal

ecoli_primer_removal_activity

Participant: Family: E. coli Pol I primer replacement implementation

Family:

E. coli Pol I primer replacement implementationPANTHER:PTHR10133:SF27

Representative Members: polA (Escherichia coli K-12)UniProtKB:P00582

Function

5'-3' exonuclease activityGO:0008409

Pol I removes primer material during nick translation; the direct biochemical substrate is phiX174 DNA.

PMID:6262323

Replication of phi X174 dna with purified enzymes. I. Conversion of viral DNA to a supercoiled, biologically active duplex.

E. coli Pol I fills a residual gap and replaces the RNA primer with DNA in a purified synthesis system.

E. coli DNA polymerase I was needed to fill the short gap left by DNA polymerase III holoenzyme, and to remove the primer and replace it with DNA.

FenA primer-flap removalMolecular Functionbacillus_fena_removal

Annotons

FenA primer-flap removal

bacillus_fena_removal_activity

Participant: Family: FenA discrete flap nucleases

Family:

FenA discrete flap nucleasesPANTHER:PTHR42646:SF2

Representative Members: fenA (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P54161

Function

5'-flap endonuclease activityGO:0017108

Discrete FenA removes flap/RNA-DNA substrates; reference168 sequence matches assayed PY79 protein.

PMID:37146086

Bacillus subtilis encodes a discrete flap endonuclease that cleaves RNA-DNA hybrids.

FenA efficiently cleaves RNA-DNA and flap substrates relevant to primer removal.

FEN is far more active than Pol I on nicked double-flap, 5' single flap, and nicked RNA-DNA hybrid substrates.

RNase HIII-PolA primer processingBiological Processbacillus_rnhc_pola_removal

Annotons

RNase HIII hybrid cleavage

rnhc_hybrid_cleavage

Participant: Family: RNase HIII proteins (InterPro IPR004641)

Family:

RNase HIII proteins (InterPro IPR004641)PANTHER:PTHR10954:SF23

Representative Members: rnhC (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:P94541

Function

RNA-DNA hybrid ribonuclease activityGO:0004523

Cuts the RNA strand of RNA-DNA hybrids; not an RNase HII complex.

PMID:30670546

RNase HIII Is Important for Okazaki Fragment Processing in Bacillus subtilis.

RNase HIII and PolA support efficient processing of a linear model Okazaki fragment in vitro.

RNase HIII and DNA polymerase I provide the primary pathway for Okazaki fragment maturation in vitro

PolA flap processing

pola_flap_processing

Participant: Family: Bacillus PolA polymerase and flap nuclease

Family:

Bacillus PolA polymerase and flap nucleasePANTHER:PTHR10133:SF27

Representative Members: polA (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:O34996

Function

5'-flap endonuclease activityGO:0017108

Processes residual primer/flap structures with RNase HIII in the demonstrated model system.

PMID:30670546

RNase HIII Is Important for Okazaki Fragment Processing in Bacillus subtilis.

RNase HIII and PolA support efficient processing of a linear model Okazaki fragment in vitro.

RNase HIII and DNA polymerase I provide the primary pathway for Okazaki fragment maturation in vitro

PMID:37146086

Bacillus subtilis encodes a discrete flap endonuclease that cleaves RNA-DNA hybrids.

Pol I is assayed on flap/RNA-DNA substrates; FenA is more active under the tested conditions.

We found that FEN is far more active than Pol I on nicked double-flap, 5' single flap, and nicked RNA-DNA hybrid substrates.

Part 9: DNA gap filling after primer removal

DNA gap filling after primer removalBiological Processdna_gap_filling

Variant set: DNA gap filling after primer removal implementations by experimentally grounded polymerase capacity with physiological-role caveats [Route] (One Or More)

PolA DNA gap fillingMolecular Functionecoli_gap_filling

Annotons

PolA DNA gap filling

ecoli_gap_filling_activity

Participant: Family: E. coli Pol I primer replacement implementation

Family:

E. coli Pol I primer replacement implementationPANTHER:PTHR10133:SF27

Representative Members: polA (Escherichia coli K-12)UniProtKB:P00582

Function

DNA-directed DNA polymerase activityGO:0003887

Fills the gap after Pol III synthesis and replaces the RNA primer with DNA.

PMID:6262323

Replication of phi X174 dna with purified enzymes. I. Conversion of viral DNA to a supercoiled, biologically active duplex.

E. coli Pol I fills a residual gap and replaces the RNA primer with DNA in a purified synthesis system.

E. coli DNA polymerase I was needed to fill the short gap left by DNA polymerase III holoenzyme, and to remove the primer and replace it with DNA.

Bacillus PolA gap-filling capacityMolecular Functionbacillus_gap_filling

Capacity of an assayed polymerase does not resolve its native contribution. Native-root satisfaction must remain unresolved when physiological gap-filling assignment is required.

Annotons

Bacillus PolA gap-filling capacity

bacillus_gap_filling_activity

Participant: Family: Bacillus PolA polymerase and flap nuclease

Family:

Bacillus PolA polymerase and flap nucleasePANTHER:PTHR10133:SF27

Representative Members: polA (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:O34996

Function

DNA-directed DNA polymerase activityGO:0003887

PolA DNA synthesis is experimentally demonstrated in vitro. Its assignment as the dominant native gap-filling polymerase remains a model; do not substitute the review-proposed PolC as established.

PMID:30670546

RNase HIII Is Important for Okazaki Fragment Processing in Bacillus subtilis.

RNase HIII and PolA support efficient processing of a linear model Okazaki fragment in vitro.

RNase HIII and DNA polymerase I provide the primary pathway for Okazaki fragment maturation in vitro

PMID:37146086

Bacillus subtilis encodes a discrete flap endonuclease that cleaves RNA-DNA hybrids.

The study proposes a FenA-removal/PolA-extension model based on the biochemical and genetic results.

we propose a model where cells remove RNA primers using FEN while upstream Okazaki fragments are extended through synthesis by Pol I.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

The dominant polymerase filling gaps after Bacillus primer removal remains unresolved; PolC is a proposal.

After primer removal, the DNAP responsible for gap filling remains poorly defined, as PolA is a mutagenic enzyme

Part 10: LigA nick sealing

LigA nick sealingMolecular Functionligation

Annotons

LigA nick sealing

ligation_activity

Participant: Family: NAD-dependent LigA ligases

Family:

NAD-dependent LigA ligasesPANTHER:PTHR23389:SF9

Representative Members: ligA (Escherichia coli K-12)UniProtKB:P15042 ligA (Pseudomonas putida KT2440)UniProtKB:Q88F25 ligA (Bacillus subtilis subsp. subtilis str. 168)UniProtKB:O31498

Function

DNA ligase (NAD+) activityGO:0003911

Seals adjacent DNA fragments only after RNA removal and DNA resynthesis.

PMID:6262323

Replication of phi X174 dna with purified enzymes. I. Conversion of viral DNA to a supercoiled, biologically active duplex.

Ligase and gyrase are needed after PolI-mediated primer replacement to obtain the completed supercoiled viral duplex.

Production of supercoiled RF required the further actions of E. coli DNA ligase and gyrase.

PMID:11095673

The NAD-dependent ligase encoded by yerG is an essential gene of Bacillus subtilis.

Bacillus YerG/LigA is the NAD-dependent ligase that supplies the essential ligase function in the tested backgrounds.

whereas yoqV did not complement the ligts defects, yerG fully complemented the growth and UV sensitivity defects of the lig mutant.

Part 11: Torsional-stress relief during fork progression

Torsional-stress relief during fork progressionBiological Processtorsional_stress_relief

Named complexes represent independently evidenced implementations. Capacity requires the correct whole complex and role-specific evidence; broad family membership or generic type-II topoisomerase chemistry does not establish both capacities. Missing implementations are unresolved panel coverage, not biological absence.

Variant set: Torsional-stress relief during fork progression implementations by demonstrated supercoiling-relief implementation [Realizer] (One Or More)

GyrAB torsional-stress reliefProtein Complexecoli_gyrab_torsional_relief

Annotons

GyrAB torsional-stress relief

torsional_stress_relief_complex

Participant: Protein Complex: GyrAB torsional-stress relief

Protein Complex:

GyrAB torsional-stress relief

Active units:

GyrA cleavage/reunion subunit2

Participant: Family: gyrA topoisomerase subunits

Family:

gyrA topoisomerase subunitsPANTHER:PTHR43493:SF5

Representative Members: gyrA (Escherichia coli K-12)UniProtKB:P0AES4

Role: Role-bearing component of the assembled GyrAB torsional-stress relief.

GyrB ATPase subunit2

Participant: Family: gyrB topoisomerase subunits

Family:

gyrB topoisomerase subunitsPANTHER:PTHR45866:SF1

Representative Members: gyrB (Escherichia coli K-12)UniProtKB:P0AES6

Role: Role-bearing component of the assembled GyrAB torsional-stress relief.

Function

DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activityGO:0003918

Assembled gyrase relieves positive supercoiling ahead of replication. Individual GyrB ATPase activity does not establish strand passage.

PMID:347446

Purification of subunits of Escherichia coli DNA gyrase and reconstitution of enzymatic activity.

Recombined GyrA and GyrB subunits restore the intrinsic reactions of gyrase, including DNA supercoiling.

The same ratio of subunits gives efficient reconstitution of the reactions intrinsic to DNA gyrase, including catalysis of supercoiling of closed duplex DNA

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

Gyrase relieves positive torsion that would otherwise prevent fork progression.

Topo II/GyrAB), which introduces (−) and relieves (+) supercoiling ahead of the RF

H37Rv GyrAB supercoiling implementationProtein Complexmyctu_gyrase_torsional_relief

Context

Mycobacterium tuberculosis H37RvNCBITaxon:83332

Full-length current targets are P9WG47/P9WG45. H37Rv genomic constructs in PMID:17038336 were sequence-verified against NC000962; tagged proteins were used. PMID:31953321 reports relatively low rates under its comparative assay conditions, so no universal enhanced-efficiency claim is made. Positive supercoiling and decatenation are separate measured capacities of the same assembled enzyme.

Annotons

H37Rv GyrAB supercoiling implementation

myctu_gyrase_torsional_relief_complex

Participant: Protein Complex: Mycobacterium tuberculosis H37Rv DNA gyrase A2B2 complex

Protein Complex:

Mycobacterium tuberculosis H37Rv DNA gyrase A2B2 complex

Active units:

H37Rv gyrA2

Participant: Family: gyrA topoisomerase subunits

Family:

gyrA topoisomerase subunitsPANTHER:PTHR43493:SF5

Representative Members: gyrA (M. tuberculosis H37Rv)UniProtKB:P9WG47

Role: Contributes to the assembled H37Rv gyrase strand-passage reaction.

H37Rv gyrB2

Participant: Family: gyrB topoisomerase subunits

Family:

gyrB topoisomerase subunitsPANTHER:PTHR45866:SF1

Representative Members: gyrB (M. tuberculosis H37Rv)UniProtKB:P9WG45

Role: Contributes to the assembled H37Rv gyrase strand-passage reaction.

Function

DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activityGO:0003918

Reconstituted H37Rv GyrA2GyrB2 supports negative supercoiling; each isolated subunit lacks whole-enzyme activity.

PMID:15047530

Mycobacterium tuberculosis DNA gyrase: interaction with quinolones and correlation with antimycobacterial drug activity.

GyrA and GyrB reconstitute supercoiling, while neither individual subunit executes it.

Neither subunit alone induced DNA supercoiling

PMID:21745817

The dimer state of GyrB is an active form: implications for the initial complex assembly and processive strand passage.

M. tuberculosis GyrB exhibits a monomer-dimer equilibrium relevant to assembly with GyrA.

These results indicate that M. tuberculosis GyrB alone exists as a monomer–dimer equilibrium in solution and this equilibrium process is slow

PMID:41255390

Indole-containing inhibitors with improved efficacy targeting the gyrase of Mycobacterium tuberculosis.

The study explicitly identifies full-length H37Rv GyrA P9WG47 and GyrB P9WG45.

encoding each full-length gyrase subunit (UniProt accession numbers P9WG47 and P9WG45, respectively).

PMID:31953321

Functional interactions between gyrase subunits are optimized in a species-specific manner.

M. tuberculosis gyrase has relatively low supercoiling and decatenation rates in this comparative study.

M. tuberculosis gyrase hydrolyzes ATP only slowly and is a poor supercoiling enzyme and decatenase.

Part 12: Daughter-DNA unlinking

Daughter-DNA unlinkingBiological Processdaughter_dna_unlinking

Variant set: Daughter-DNA unlinking implementations by demonstrated decatenation implementation [Realizer] (One Or More)

ParCE daughter-DNA unlinkingProtein Complexecoli_parce_decatenation

Annotons

ParCE daughter-DNA unlinking

daughter_dna_unlinking_complex

Participant: Protein Complex: ParCE daughter-DNA unlinking

Protein Complex:

ParCE daughter-DNA unlinking

Active units:

ParC cleavage/reunion subunit2

Participant: Family: parC topoisomerase subunits

Family:

parC topoisomerase subunitsPANTHER:PTHR43493:SF1

Representative Members: parC (Escherichia coli K-12)UniProtKB:P0AFI2

Role: Role-bearing component of the assembled ParCE daughter-DNA unlinking.

ParE ATPase subunit2

Participant: Family: parE topoisomerase subunits

Family:

parE topoisomerase subunitsPANTHER:PTHR45866:SF4

Representative Members: parE (Escherichia coli K-12)UniProtKB:P20083

Role: Role-bearing component of the assembled ParCE daughter-DNA unlinking.

Function

DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activityGO:0003918

Assembled topoisomerase IV decatenates replicated DNA in the sampled circular-chromosome route. These exact enzymes are not universal bacterial requirements.

PMID:8227000

Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions.

Topoisomerase IV activity resides in a ParC2-ParE2 complex.

the active form of Topo IV was a heterotetramer, ParC2ParE2.

PMID:8104339

Decatenation activity of topoisomerase IV during oriC and pBR322 DNA replication in vitro.

TopoIV resolves linked daughter DNA in reconstituted oriC/pBR322 replication, whereas gyrase chiefly relieves positive supercoiling.

These results suggest that during DNA replication, gyrase acts primarily to relieve accumulated positive supercoiling and Topo IV acts to segregate the daughter chromosomes.

H37Rv GyrAB decatenation implementationProtein Complexmyctu_gyrase_decatenation

Context

Mycobacterium tuberculosis H37RvNCBITaxon:83332

Annotons

H37Rv GyrAB decatenation implementation

myctu_gyrase_decatenation_complex

Participant: Protein Complex: Mycobacterium tuberculosis H37Rv DNA gyrase A2B2 complex

Protein Complex:

Mycobacterium tuberculosis H37Rv DNA gyrase A2B2 complex

Active units:

H37Rv gyrA2

Participant: Family: gyrA topoisomerase subunits

Family:

gyrA topoisomerase subunitsPANTHER:PTHR43493:SF5

Representative Members: gyrA (M. tuberculosis H37Rv)UniProtKB:P9WG47

Role: Contributes to the assembled H37Rv gyrase strand-passage reaction.

H37Rv gyrB2

Participant: Family: gyrB topoisomerase subunits

Family:

gyrB topoisomerase subunitsPANTHER:PTHR45866:SF1

Representative Members: gyrB (M. tuberculosis H37Rv)UniProtKB:P9WG45

Role: Contributes to the assembled H37Rv gyrase strand-passage reaction.

Function

DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activityGO:0003918

Reconstituted H37Rv GyrA2GyrB2 supports kDNA decatenation. Its contribution to native daughter-DNA unlinking is physiological inference, not a measured chromosome-segregation phenotype.

PMID:17038336

The key DNA-binding residues in the C-terminal domain of Mycobacterium tuberculosis DNA gyrase A subunit (GyrA).

Reconstituted H37Rv GyrA/GyrB directly decatenates kDNA; wild type remains active at the low concentration where selected GyrA mutants fail.

However, lowering gyrase concentration to 0.01 μM, mutants of D669A, R691A, G729A and R745A showed no decatenation activity, whereas the wild-type enzyme and E514A still had (Figure 8C).

PMID:21745817

The dimer state of GyrB is an active form: implications for the initial complex assembly and processive strand passage.

M. tuberculosis GyrB exhibits a monomer-dimer equilibrium relevant to assembly with GyrA.

These results indicate that M. tuberculosis GyrB alone exists as a monomer–dimer equilibrium in solution and this equilibrium process is slow

PMID:41255390

Indole-containing inhibitors with improved efficacy targeting the gyrase of Mycobacterium tuberculosis.

The study explicitly identifies full-length H37Rv GyrA P9WG47 and GyrB P9WG45.

encoding each full-length gyrase subunit (UniProt accession numbers P9WG47 and P9WG45, respectively).

PMID:31953321

Functional interactions between gyrase subunits are optimized in a species-specific manner.

M. tuberculosis gyrase has relatively low supercoiling and decatenation rates in this comparative study.

M. tuberculosis gyrase hydrolyzes ATP only slowly and is a poor supercoiling enzyme and decatenase.

Part: HolC-HolD clamp-loader accessory context (optional)

HolC-HolD clamp-loader accessory contextBiological Processholc_hold_accessory

Annotons

HolC accessory adaptor

holc_adaptor

Participant: Family: HolC chi accessory adaptors

Family:

HolC chi accessory adaptorsPANTHER:PTHR38767:SF1

Representative Members: holC (Escherichia coli K-12)UniProtKB:P28905 holC (Pseudomonas putida KT2440)UniProtKB:Q88P74

Function

protein-macromolecule adaptor activityGO:0030674

Links SSB-associated templates with loader partners; not required in every minimal purified loader.

PMID:16210315

Discovery and characterization of the cryptic psi subunit of the pseudomonad DNA replicase.

Cognate Pseudomonas chi/psi strongly stimulates the minimal loader and permits activity under physiological salt conditions.

P. aeruginosa chiPsi increased the specific activity of tau(3)deltadelta' 25-fold and enabled the holoenzyme to function under physiological salt conditions.

PMID:14717711

Crystal structure of the chi:psi sub-assembly of the Escherichia coli DNA polymerase clamp-loader complex.

The E. coli chi-psi heterodimer bridges SSB with the clamp loader; this is complex-level bridging evidence for the HolC adaptor role.

In E. coli, the chi:psi heterodimer serves as a bridge between the clamp-loader complex and the single-stranded DNA-binding protein.

Pseudomonas HolD psi contribution

hold_accessory

Participant: Family: Divergent Pseudomonas HolD psi accessory family

Family:

Divergent Pseudomonas HolD psi accessory family

Representative Members: holD (Pseudomonas putida KT2440)UniProtKB:Q88Q02

Contributes to the assembled clamp loader. The verified KT2440 locus is PP_0696/Q88Q02, not PP_0978; native TTG start and experimental fusion differ from the longer database translation. No independent clamp-loader MF is assigned.

PMID:21955458

Characterization of the χψ subcomplex of Pseudomonas aeruginosa DNA polymerase III.

The KT2440 chi/psi complex has DNA-binding activity that can support an SSB-DNA-associated accessory role.

We also observed DNA-binding activity for P. putida χψ

PMID:16210315

Discovery and characterization of the cryptic psi subunit of the pseudomonad DNA replicase.

P. aeruginosa chi-psi stimulates its loader under physiological salt conditions; this is comparative mechanism evidence for the mapped KT2440 HolD, not isolated KT2440 catalysis.

aeruginosa chiPsi increased the specific activity of tau(3)deltadelta' 25-fold and enabled the holoenzyme to function under physiological salt conditions.

PMID:17210572

A function for the psi subunit in loading the Escherichia coli DNA polymerase sliding clamp.

Comparative psi mechanism supports stabilization of the ATP-induced DNA-binding loader state.

The psi subunit is important for stabilizing an ATP-induced conformational state with high affinity for DNA

Part: Tau-specific replisome coupling (optional)

Tau-specific replisome couplingMolecular Functiontau_coupling

Annotons

Tau-specific replisome coupling

tau_coupling_activity

Participant: Family: Full-length tau scaffolding form of DnaX

Family:

Full-length tau scaffolding form of DnaXPANTHER:PTHR11669:SF0

Representative Members: dnaX (Escherichia coli K-12)UniProtKB:P06710

Function

protein complex scaffold activityGO:0140378

Tau-specific C-terminal regions tether polymerase and helicase; the gamma form lacks these regions.

PMID:42133467

Mechanisms of chromosomal DNA replication in Escherichia coli and Bacillus subtilis.

Full-length tau couples the leading-strand polymerase to the helicase.

the leading-strand Pol III core enzyme is physically linked to DnaB through DnaX/τ interactions