Bacteriophage Genome Replication, Transcriptional Takeover, and Counter-Defense

A reusable module capturing the intracellular phage replication and host takeover program across major Baltimore classes of bacteriophages: (1) genome replication (`GO:0039693`, `GO:0039694`) modeled as a variant set across bidirectional theta + recombination-dependent dsDNA replication (`GO:0039686`, e.g. T4, early lambda, T7), rolling-circle dsDNA/ssDNA replication (`GO:0039683`, e.g. phiX174 gpA, M13 pII, late lambda, P2 gpA), protein-primed linear dsDNA replication (`GO:0039693`, `GO:0003887`, phi29 gp2/gp3, PRD1 P1/P8), and RNA-directed RNA replication (`GO:0039694`, `GO:0003968`, e.g. MS2/Qbeta replicase, phi6 P2); (2) an optional viral transcriptional takeover and translational cascade part (`GO:0019083`, `GO:0019080`, `GO:0039653`, `GO:0031564`), modeled as a variant set across transcription antitermination (lambda N/Q, P4 Psu), host RNAP sigma-factor remodeling or inhibition coupled to phage-encoded single-subunit RNA polymerases (T4 AsiA/gp55, T7 gp1/gp2), and direct (+)ssRNA translational regulation (MS2, Qbeta), whereas small ssDNA phages (phiX174, M13) that rely on unmodified host RNAP without a phage-encoded takeover or translational regulator omit this optional part; and (3) an optional host chromosome degradation (`GO:0099015`, T4 denA/ndd, gp46/gp47) and evasion of host restriction-modification and nuclease defenses (`GO:0099018`, T4 agt/bgt, Arn, Stp, T7 Ocr) part.

MODULE:phage_genome_replication_and_transcriptionCOMPLETECONCRETEBiological Processmodules/phage_genome_replication_and_transcription.yaml
viral DNA genome replicationGO:0039693 viral RNA genome replicationGO:0039694 viral transcriptionGO:0019083 symbiont-mediated evasion of host restriction-modification systemGO:0099018
PMID:7806534
A role for two DNA helicases in the replication of T4 bacteriophage DNA.
Bacteriophage T4 DNA replication employs both the replicative hexameric helicase gp41 and the accessory helicase Dda, together with UvsW and the gp46/gp47 recombination nuclease complex, to drive origin-initiated and recombination-dependent DNA synthesis.
The T4 bacteriophage gene 41 protein is the highly processive DNA helicase of the T4 primosome, a central part of the protein machinery that moves the T4 DNA replication fork.
PMID:17823128
The phage T4 protein UvsW drives Holliday junction branch migration.
Phage T4 UvsW is an ATP-dependent DNA/RNA helicase that catalyzes Holliday junction branch migration during recombination-dependent DNA replication and repair.
The phage T4 UvsW protein has been shown to play a crucial role in the switch from origin-dependent to recombination-dependent replication in T4 infections through the unwinding of origin R-loop initiation intermediates.
PMID:6078540
On the specificity of bacteriophage-induced hydroxymethylcytosine glucosyltransferases. II. Specificities of hydroxymethylcytosine alphaand beta-glucosyltransferases induced by bacteriophage T4.
Bacteriophage T4 alpha- and beta-glucosyltransferases (agt and bgt) glucosylate 5-hydroxymethylcytosine residues in phage DNA to protect the viral genome from host restriction endonucleases.
PMID:38989624
Ocr-mediated suppression of BrxX unveils a phage counter-defense mechanism.
Phage DNA mimic proteins such as T7 Ocr and T4 Arn inhibit bacterial restriction-modification and BREX defense systems.
Cryo-electron microscopy and biophysical analyses reveal that Ocr, a DNA mimic, forms a stable complex with BrxX, highlighting a conserved interaction interface across diverse BrxX variants.
file:projects/PHAGES.md
Bacteriophage Genome & Module Curation Plan
Defines the genome replication, transcriptional takeover, and anti-defense variant architecture across dsDNA, ssDNA, ssRNA, and dsRNA phages.
every plaque-forming phage must execute host attachment, genome entry, replication/transcription, virion assembly, and host release—either via phage-encoded proteins, non-orthologous displacements hidden in "viral dark matter," or explicit hijacking of host machinery.

Curated for the Bacteriophage Genome & Module Curation project. Integrates with `MODULE:anti_crispr_suppression` for anti-CRISPR (`GO:0098672`) proteins while directly capturing restriction-modification/McrBC evasion (`GO:0099018`) and host chromosome degradation (`GO:0099015`).

10Nodes
2Parts
2Variant Sets
7Variants
9Annotons
0Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:phage_genome_replication_and_transcription 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

0 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (8 comparison(s))

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

AnnotonParticipantFunctionAssessment
host_chromosome_degradation ANY_WITH_FUNCTION
Gene 		endodeoxyribonuclease activity
GO:0004520 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
anti_restriction_dna_modification_and_mimicry ANY_PARTICIPANT
Gene 		glucosyltransferase activity
GO:0046527 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
antitermination_factor_activity ANY_PARTICIPANT
Gene 		transcription regulator activity
GO:0140110 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
host_transcription_shutoff_and_viral_rnap_activity ANY_WITH_FUNCTION
Gene 		DNA-directed RNA polymerase activity
GO:0003899 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
dsdna_replisome_and_rdr_helicase ANY_WITH_FUNCTION
Gene 		DNA helicase activity
GO:0003678 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
rolling_circle_initiator_endonuclease ANY_WITH_FUNCTION
Gene 		endodeoxyribonuclease activity
GO:0004520 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
viral_rdrp_activity ANY_WITH_FUNCTION
Gene 		RNA-directed RNA polymerase activity
GO:0003968 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
protein_primed_dna_polymerase ANY_WITH_FUNCTION
Gene 		DNA-directed DNA polymerase activity
GO:0003887 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.

Gene-review completeness (9/9 grounded genes reviewed)

9 complete review(s) · 3 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
1 P00573 ✓ ✓ ✗
2 P03680 ✓ ✓ ✗
41 P04530 ✓ ✓ ✓
A P03631 ✓ ✓ ✗
agt P04519 ✓ ✓ ✓
cp P03612 ✓ ✓ ✗
denA P07059 ✓ ✓ ✓
N P03045 ✓ ✓ ✗
rep P00585 ✓ ✓ ✗

Details

Context
VirusesNCBITaxon:10239 BacteriaNCBITaxon:2
Bacteriophage Genome Replication, Transcriptional Takeover, and Counter-DefenseBiological Processphage_genome_replication_and_transcription
viral DNA genome replicationGO:0039693 viral RNA genome replicationGO:0039694 viral transcriptionGO:0019083 symbiont-mediated evasion of host restriction-modification systemGO:0099018
Context
VirusesNCBITaxon:10239 BacteriaNCBITaxon:2
Part 1: host chromosome degradation and restriction-modification counter-defense (optional)
Host chromosome degradation, DNA modification, and anti-restrictionBiological Processhost_takeover_and_counter_defense

Early phage proteins shut down competing host processes and protect viral DNA: nucleoid-disruption and endonuclease complexes (T4 Ndd, DenA, DenB, and gp46/gp47 Mre11-Rad50 nuclease) degrade host DNA into dNMP precursors (`GO:0099015`), while glucosyltransferases (T4 Agt, Bgt), DNA-mimic proteins (T4 Arn, T7 Ocr), and anti-anticodon-nuclease peptides (T4 Stp) evade host restriction systems (`GO:0099018`).

Annotons

Phage-mediated disruption and degradation of the host chromosome
host_chromosome_degradation
Participant: Any With Function: denA (Bacteriophage T4)
Gene Product:
denA (Bacteriophage T4)UniProtKB:P07059
Required Function:
endodeoxyribonuclease activityGO:0004520
Phage nucleoid disruption proteins (T4 Ndd) and host-DNA-degrading nucleases (T4 DenA endonuclease II, DenB endonuclease IV, and gp46/gp47 exonuclease complex).

Function

endodeoxyribonuclease activityGO:0004520

Processes

degradation of host chromosome by virusGO:0099015

Locations

host cell cytoplasmGO:0030430

Nicks and degrades the unmodified host bacterial chromosome to shut off host gene expression and recycle nucleotides for phage DNA synthesis.

Evasion of host restriction-modification systems by DNA glucosylation or mimicry
anti_restriction_dna_modification_and_mimicry
Participant: Any Participant: agt (Bacteriophage T4)
Gene Product:
agt (Bacteriophage T4)UniProtKB:P04519
HMC glucosyltransferases (T4 Agt and Bgt), DNA-mimic anti-restriction proteins (T4 Arn targeting McrBC; T7 Ocr targeting Type I R-M and BREX), and host-defense modulators (T4 Stp, AdfA).

Function

glucosyltransferase activityGO:0046527

Processes

symbiont-mediated evasion of host restriction-modification systemGO:0099018

Locations

host cell cytoplasmGO:0030430

Covalently modifies phage DNA or directly inhibits host restriction endonucleases to prevent viral genome cleavage.

PMID:6078540
T4 alpha- and beta-glucosyltransferases transfer glucose to hydroxymethylcytosine in phage DNA.
Part 2: phage-encoded transcriptional takeover or translational cascade strategy (optional)
Phage transcriptional takeover and translational cascadeBiological Processtranscriptional_takeover_and_cascade

Optional phage-encoded program that redirects host transcription or regulates viral mRNA translation; omitted in small ssDNA phages (phiX174, M13) that rely entirely on unmodified host sigma70 RNA polymerase without a phage-encoded transcriptional takeover or translational regulator.

Variant set: Bacteriophage transcriptional takeover and cascade strategy by host RNAP antitermination/remodeling vs. phage-encoded RNAP vs. direct (+)ssRNA translational regulation (Exactly One)

Phages with dedicated gene-expression regulators act by modifying host RNAP termination/promoter specificity, by encoding their own RNA polymerase, or—in (+)ssRNA phages—by translating the positive-sense RNA genome directly with coat-protein-mediated translational control; small ssDNA phages (phiX174, M13) that rely solely on unmodified host RNAP without a phage-encoded transcriptional takeover factor or translational regulator omit this optional part (`optional: true`).

Transcription antitermination cascade (lambda N/Q and P4 Psu-type)Biological Processtranscription_antitermination_cascade

Phage-encoded antitermination proteins modify elongating host RNA polymerase (lambda N recognizing nut RNA sites with NusA/B/E/G; lambda Q recognizing qut DNA elements at pR'; or satellite P4 Psu directly inhibiting host Rho helicase) to read through intrinsic and Rho-dependent terminators (`GO:0031564`, `GO:0019083`).

Annotons

Phage transcription antitermination factor activity
antitermination_factor_activity
Participant: Any Participant: N (Escherichia phage lambda)
Gene Product:
N (Escherichia phage lambda)UniProtKB:P03045
Early and late phage transcription antiterminators (lambda N, lambda Q, P22 gp24/gp23, P4 Psu).

Function

transcription regulator activityGO:0140110

Processes

transcription antiterminationGO:0031564 viral transcriptionGO:0019083

Locations

host cell cytoplasmGO:0030430

Renders host RNA polymerase termination-resistant to express delayed-early and late phage operons.

Host RNAP shutoff coupled to phage-encoded RNA polymerase or sigma remodeling (T7/T4-type)Biological Processhost_rnap_shutoff_and_viral_rnap

Phages inhibit host sigma70-dependent transcription (`GO:0039653`, e.g. T7 gp2 binding the host RNAP beta' jaw, or T4 AsiA/Alc/gp55 remodeling host RNAP) and drive middle/late viral transcription (`GO:0019083`) via a phage-encoded single-subunit RNA polymerase (T7 gp1) or phage sigma factors.

Annotons

Suppression of host transcription and phage-specific transcription
host_transcription_shutoff_and_viral_rnap_activity
Participant: Any With Function: 1 (Enterobacteria phage T7)
Gene Product:
1 (Enterobacteria phage T7)UniProtKB:P00573
Required Function:
DNA-directed RNA polymerase activityGO:0003899
Phage-encoded single-subunit RNA polymerase (T7 gp1) paired with host RNAP inhibitors (T7 gp2, gp0.7) or sigma-factor remodeling proteins (T4 AsiA, MotA, gp55).

Function

DNA-directed RNA polymerase activityGO:0003899

Processes

viral transcriptionGO:0019083 symbiont-mediated suppression of host transcriptionGO:0039653

Locations

host cell cytoplasmGO:0030430

Redirects cellular ribonucleotide pools exclusively to middle and late viral mRNA synthesis.

Direct (+)ssRNA translational regulation without host RNAP takeover (MS2/Qbeta-type)Biological Processhost_rnap_or_direct_translation_without_takeover

Positive-sense ssRNA leviviruses (MS2, Qbeta) bypass DNA-dependent transcription entirely and translate their genomic (+)RNA directly as mRNA coupled to coat-mediated translational repression (`GO:0019080`) without a host RNAP takeover factor.

Annotons

Direct (+)ssRNA viral translational regulation
basal_viral_transcription_or_translation
Participant: Any Participant: cp (Emesvirus zinderi)
Gene Product:
cp (Emesvirus zinderi)UniProtKB:P03612
Viral translational regulators (such as MS2 cp and Qbeta cp coat proteins binding the replicase operator hairpin) that govern viral gene expression (`GO:0019080`) without host RNAP takeover factors.

Processes

viral gene expressionGO:0019080

Locations

host cell cytoplasmGO:0030430

Regulates translation of genomic (+)ssRNA without dedicated host RNAP takeover factors.

Variant set: Bacteriophage genome replication strategy by nucleic acid type and replisome initiation mechanism (Exactly One)

Bacteriophages replicate their genomes using one of four major enzymatic strategies depending on genome topology and Baltimore class.

Bidirectional theta and recombination-dependent dsDNA replication (T4/lambda-early/T7-type)Biological Processbidirectional_theta_and_rdr_dsdna_replication

Origin-initiated bidirectional replication (`GO:0039686`) driven by a phage replisome (such as T4 gp43 DNA polymerase, gp41 replicative helicase, gp61 primase, gp32 SSB, Dda accessory helicase) or host DnaB recruited by lambda O/P, transitioning in T4 to recombination-dependent replication (RDR) mediated by UvsX, UvsY, UvsW (`PMID:17823128`), and the gp46/gp47 recombination nuclease.

Annotons

Replicative DNA helicase, accessory helicase, and recombination-dependent replication
dsdna_replisome_and_rdr_helicase
Participant: Any With Function: 41 (Bacteriophage T4)
Gene Product:
41 (Bacteriophage T4)UniProtKB:P04530
Required Function:
DNA helicase activityGO:0003678
Replicative hexameric DNA helicase (T4 gp41, T7 gp4), accessory 5'-3' DNA helicase (T4 Dda), Holliday junction branch-migration helicase (T4 UvsW), and recombination nuclease complex (T4 gp46/gp47).

Function

DNA helicase activityGO:0003678

Processes

bidirectional double-stranded viral DNA replicationGO:0039686 viral DNA genome replicationGO:0039693

Locations

host cell cytoplasmGO:0030430

Unwinds duplex viral DNA at replication forks and drives recombination-dependent concatemer synthesis.

PMID:7806534
T4 gp41 and Dda DNA helicases cooperate during bacteriophage T4 DNA replication.
The T4 bacteriophage gene 41 protein is the highly processive DNA helicase of the T4 primosome, a central part of the protein machinery that moves the T4 DNA replication fork.
Rolling-circle nicking endonuclease DNA replication (phiX174/M13/P2/lambda-late-type)Biological Processrolling_circle_dna_replication

A site-specific HUH or tyrosine relaxase/endonuclease (phiX174 gpA, M13 pII, P2 gpA) introduces a single-strand nick at the viral origin to prime 3'-OH rolling-circle synthesis (`GO:0039683`), or late lambda Gam inhibits host RecBCD (`GO:0098673`) to allow rolling-circle concatemer formation.

Annotons

Rolling-circle replication initiator endonuclease activity
rolling_circle_initiator_endonuclease
Participant: Any With Function: A (Escherichia phage phiX174)
Gene Product:
A (Escherichia phage phiX174)UniProtKB:P03631
Required Function:
endodeoxyribonuclease activityGO:0004520
Origin-specific nicking-closing endonucleases (phiX174 gpA, M13 pII, P2 gpA) and rolling-circle ssDNA-binding proteins (M13 pV).

Function

endodeoxyribonuclease activityGO:0004520

Processes

rolling circle double-stranded viral DNA replicationGO:0039683

Locations

host cell cytoplasmGO:0030430

Nicks the double-stranded replicative form (RF) origin to initiate rolling-circle strand displacement synthesis.

Viral RNA-directed RNA polymerase genome replication (MS2/Qbeta/phi6-type)Biological Processrna_directed_rna_replication

Single-stranded (Fiersviridae MS2, Qbeta) and double-stranded (Cystoviridae phi6 P2) RNA phages encode an RNA-directed RNA polymerase (`GO:0003968`) that replicates the viral RNA genome (`GO:0039694`), often recruiting host translation factors EF-Tu, EF-Ts, and ribosomal protein S1 into the replicase holoenzyme.

Annotons

Phage RNA-directed RNA polymerase catalytic activity
viral_rdrp_activity
Participant: Any With Function: rep (Emesvirus zinderi)
Gene Product:
rep (Emesvirus zinderi)UniProtKB:P00585
Required Function:
RNA-directed RNA polymerase activityGO:0003968
Viral RNA-directed RNA polymerase catalytic subunit (MS2 rep, Qbeta rep, phi6 P2).

Function

RNA-directed RNA polymerase activityGO:0003968

Processes

viral RNA genome replicationGO:0039694

Locations

host cell cytoplasmGO:0030430

Synthesizes complementary minus-strand and progeny plus-strand viral RNA genomes.

Protein-primed linear dsDNA replication (phi29/PRD1-type)Biological Processprotein_primed_linear_dsdna_replication

Linear dsDNA phages with covalently linked 5' terminal proteins (such as Bacillus phage phi29 gp2 DNA polymerase / gp3 terminal protein and Tectivirus PRD1 P1 DNA polymerase / P8 terminal protein) initiate replication by protein-primed deoxynucleotidylation and continuous strand-displacement synthesis (`GO:0039693`, `GO:0003887`).

Annotons

Protein-primed strand-displacing DNA polymerase activity
protein_primed_dna_polymerase
Participant: Any With Function: 2 (Bacillus phage phi29)
Gene Product:
2 (Bacillus phage phi29)UniProtKB:P03680
Required Function:
DNA-directed DNA polymerase activityGO:0003887
Family B protein-primed DNA polymerase (phi29 gp2, PRD1 P1) and covalent 5' terminal primer protein (phi29 gp3, PRD1 P8) that initiate linear dsDNA synthesis from genome termini.

Function

DNA-directed DNA polymerase activityGO:0003887

Processes

viral DNA genome replicationGO:0039693

Locations

host cell cytoplasmGO:0030430

Catalyzes protein-primed initiation and continuous strand-displacement replication of linear dsDNA genomes.