id: MODULE:phage_genome_replication_and_transcription title: Bacteriophage Genome Replication, Transcriptional Takeover, and Counter-Defense description: '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.' status: COMPLETE scope: CONCRETE evidence: - source_id: PMID:7806534 title: A role for two DNA helicases in the replication of T4 bacteriophage DNA. statement: 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. supporting_text: 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. - source_id: PMID:17823128 title: The phage T4 protein UvsW drives Holliday junction branch migration. statement: Phage T4 UvsW is an ATP-dependent DNA/RNA helicase that catalyzes Holliday junction branch migration during recombination-dependent DNA replication and repair. supporting_text: 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. - source_id: PMID:6078540 title: On the specificity of bacteriophage-induced hydroxymethylcytosine glucosyltransferases. II. Specificities of hydroxymethylcytosine alphaand beta-glucosyltransferases induced by bacteriophage T4. statement: 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. - source_id: PMID:38989624 title: Ocr-mediated suppression of BrxX unveils a phage counter-defense mechanism. statement: Phage DNA mimic proteins such as T7 Ocr and T4 Arn inhibit bacterial restriction-modification and BREX defense systems. supporting_text: 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. - source_id: file:projects/PHAGES.md title: Bacteriophage Genome & Module Curation Plan statement: Defines the genome replication, transcriptional takeover, and anti-defense variant architecture across dsDNA, ssDNA, ssRNA, and dsRNA phages. supporting_text: 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. notes: 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`). module: id: phage_genome_replication_and_transcription label: Bacteriophage Genome Replication, Transcriptional Takeover, and Counter-Defense module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: viral DNA genome replication term: id: GO:0039693 label: viral DNA genome replication description: Replication of a DNA bacteriophage genome via theta, rolling-circle, recombination-dependent, or protein-primed mechanisms. - preferred_term: viral RNA genome replication term: id: GO:0039694 label: viral RNA genome replication description: Replication of an single-stranded or double-stranded RNA bacteriophage genome by a phage-encoded RNA-directed RNA polymerase. - preferred_term: viral transcription term: id: GO:0019083 label: viral transcription description: Transcription of early, middle, and late bacteriophage genes using host or phage-encoded RNA polymerase. - preferred_term: symbiont-mediated evasion of host restriction-modification system term: id: GO:0099018 label: symbiont-mediated evasion of host restriction-modification system description: Protection of the phage genome from bacterial restriction nucleases via covalent DNA modification or DNA-mimic proteins. context: taxa: - preferred_term: Viruses term: id: NCBITaxon:10239 label: Viruses - preferred_term: Bacteria term: id: NCBITaxon:2 label: Bacteria parts: - order: 1 role: host chromosome degradation and restriction-modification counter-defense node: id: host_takeover_and_counter_defense label: Host chromosome degradation, DNA modification, and anti-restriction module_type: BIOLOGICAL_PROCESS description: '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: - id: host_chromosome_degradation label: Phage-mediated disruption and degradation of the host chromosome participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: endodeoxyribonuclease activity term: id: GO:0004520 label: endodeoxyribonuclease activity gene_product: preferred_term: denA (Bacteriophage T4) term: id: UniProtKB:P07059 label: Endonuclease II description: Phage nucleoid disruption proteins (T4 Ndd) and host-DNA-degrading nucleases (T4 DenA endonuclease II, DenB endonuclease IV, and gp46/gp47 exonuclease complex). function: preferred_term: endodeoxyribonuclease activity term: id: GO:0004520 label: endodeoxyribonuclease activity processes: - preferred_term: degradation of host chromosome by virus term: id: GO:0099015 label: degradation of host chromosome by virus locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Nicks and degrades the unmodified host bacterial chromosome to shut off host gene expression and recycle nucleotides for phage DNA synthesis. - id: anti_restriction_dna_modification_and_mimicry label: Evasion of host restriction-modification systems by DNA glucosylation or mimicry participant: selector_type: ANY_PARTICIPANT gene_product: preferred_term: agt (Bacteriophage T4) term: id: UniProtKB:P04519 label: DNA alpha-glucosyltransferase description: 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: preferred_term: glucosyltransferase activity term: id: GO:0046527 label: glucosyltransferase activity processes: - preferred_term: symbiont-mediated evasion of host restriction-modification system term: id: GO:0099018 label: symbiont-mediated evasion of host restriction-modification system locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm evidence: - source_id: PMID:6078540 statement: T4 alpha- and beta-glucosyltransferases transfer glucose to hydroxymethylcytosine in phage DNA. role_description: Covalently modifies phage DNA or directly inhibits host restriction endonucleases to prevent viral genome cleavage. optional: true - order: 2 role: phage-encoded transcriptional takeover or translational cascade strategy node: id: transcriptional_takeover_and_cascade label: Phage transcriptional takeover and translational cascade module_type: BIOLOGICAL_PROCESS description: 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_sets: - id: transcriptional_takeover_strategy label: Bacteriophage transcriptional takeover and cascade strategy axis: host RNAP antitermination/remodeling vs. phage-encoded RNAP vs. direct (+)ssRNA translational regulation selection: EXACTLY_ONE notes: '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`).' variants: - id: transcription_antitermination_cascade label: Transcription antitermination cascade (lambda N/Q and P4 Psu-type) module_type: BIOLOGICAL_PROCESS description: 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: - id: antitermination_factor_activity label: Phage transcription antitermination factor activity participant: selector_type: ANY_PARTICIPANT gene_product: preferred_term: N (Escherichia phage lambda) term: id: UniProtKB:P03045 label: Antitermination protein N description: Early and late phage transcription antiterminators (lambda N, lambda Q, P22 gp24/gp23, P4 Psu). function: preferred_term: transcription regulator activity term: id: GO:0140110 label: transcription regulator activity processes: - preferred_term: transcription antitermination term: id: GO:0031564 label: transcription antitermination - preferred_term: viral transcription term: id: GO:0019083 label: viral transcription locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Renders host RNA polymerase termination-resistant to express delayed-early and late phage operons. - id: host_rnap_shutoff_and_viral_rnap label: Host RNAP shutoff coupled to phage-encoded RNA polymerase or sigma remodeling (T7/T4-type) module_type: BIOLOGICAL_PROCESS description: 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: - id: host_transcription_shutoff_and_viral_rnap_activity label: Suppression of host transcription and phage-specific transcription participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: DNA-directed RNA polymerase activity term: id: GO:0003899 label: DNA-directed RNA polymerase activity gene_product: preferred_term: 1 (Enterobacteria phage T7) term: id: UniProtKB:P00573 label: T7 RNA polymerase description: 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: preferred_term: DNA-directed RNA polymerase activity term: id: GO:0003899 label: DNA-directed RNA polymerase activity processes: - preferred_term: viral transcription term: id: GO:0019083 label: viral transcription - preferred_term: symbiont-mediated suppression of host transcription term: id: GO:0039653 label: symbiont-mediated suppression of host transcription locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Redirects cellular ribonucleotide pools exclusively to middle and late viral mRNA synthesis. - id: host_rnap_or_direct_translation_without_takeover label: Direct (+)ssRNA translational regulation without host RNAP takeover (MS2/Qbeta-type) module_type: BIOLOGICAL_PROCESS description: 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: - id: basal_viral_transcription_or_translation label: Direct (+)ssRNA viral translational regulation participant: selector_type: ANY_PARTICIPANT gene_product: preferred_term: cp (Emesvirus zinderi) term: id: UniProtKB:P03612 label: Capsid protein description: 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: - preferred_term: viral gene expression term: id: GO:0019080 label: viral gene expression locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Regulates translation of genomic (+)ssRNA without dedicated host RNAP takeover factors. optional: true variant_sets: - id: genome_replication_strategy label: Bacteriophage genome replication strategy axis: nucleic acid type and replisome initiation mechanism selection: EXACTLY_ONE notes: Bacteriophages replicate their genomes using one of four major enzymatic strategies depending on genome topology and Baltimore class. variants: - id: bidirectional_theta_and_rdr_dsdna_replication label: Bidirectional theta and recombination-dependent dsDNA replication (T4/lambda-early/T7-type) module_type: BIOLOGICAL_PROCESS description: 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: - id: dsdna_replisome_and_rdr_helicase label: Replicative DNA helicase, accessory helicase, and recombination-dependent replication participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: DNA helicase activity term: id: GO:0003678 label: DNA helicase activity gene_product: preferred_term: 41 (Bacteriophage T4) term: id: UniProtKB:P04530 label: DnaB-like replicative helicase description: 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: preferred_term: DNA helicase activity term: id: GO:0003678 label: DNA helicase activity processes: - preferred_term: bidirectional double-stranded viral DNA replication term: id: GO:0039686 label: bidirectional double-stranded viral DNA replication - preferred_term: viral DNA genome replication term: id: GO:0039693 label: viral DNA genome replication locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm evidence: - source_id: PMID:7806534 statement: T4 gp41 and Dda DNA helicases cooperate during bacteriophage T4 DNA replication. supporting_text: 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. role_description: Unwinds duplex viral DNA at replication forks and drives recombination-dependent concatemer synthesis. - id: rolling_circle_dna_replication label: Rolling-circle nicking endonuclease DNA replication (phiX174/M13/P2/lambda-late-type) module_type: BIOLOGICAL_PROCESS description: 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: - id: rolling_circle_initiator_endonuclease label: Rolling-circle replication initiator endonuclease activity participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: endodeoxyribonuclease activity term: id: GO:0004520 label: endodeoxyribonuclease activity gene_product: preferred_term: A (Escherichia phage phiX174) term: id: UniProtKB:P03631 label: Replication-associated protein A description: Origin-specific nicking-closing endonucleases (phiX174 gpA, M13 pII, P2 gpA) and rolling-circle ssDNA-binding proteins (M13 pV). function: preferred_term: endodeoxyribonuclease activity term: id: GO:0004520 label: endodeoxyribonuclease activity processes: - preferred_term: rolling circle double-stranded viral DNA replication term: id: GO:0039683 label: rolling circle double-stranded viral DNA replication locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Nicks the double-stranded replicative form (RF) origin to initiate rolling-circle strand displacement synthesis. - id: rna_directed_rna_replication label: Viral RNA-directed RNA polymerase genome replication (MS2/Qbeta/phi6-type) module_type: BIOLOGICAL_PROCESS description: 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: - id: viral_rdrp_activity label: Phage RNA-directed RNA polymerase catalytic activity participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: RNA-directed RNA polymerase activity term: id: GO:0003968 label: RNA-directed RNA polymerase activity gene_product: preferred_term: rep (Emesvirus zinderi) term: id: UniProtKB:P00585 label: RNA-directed RNA polymerase beta chain description: Viral RNA-directed RNA polymerase catalytic subunit (MS2 rep, Qbeta rep, phi6 P2). function: preferred_term: RNA-directed RNA polymerase activity term: id: GO:0003968 label: RNA-directed RNA polymerase activity processes: - preferred_term: viral RNA genome replication term: id: GO:0039694 label: viral RNA genome replication locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Synthesizes complementary minus-strand and progeny plus-strand viral RNA genomes. - id: protein_primed_linear_dsdna_replication label: Protein-primed linear dsDNA replication (phi29/PRD1-type) module_type: BIOLOGICAL_PROCESS description: 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: - id: protein_primed_dna_polymerase label: Protein-primed strand-displacing DNA polymerase activity participant: selector_type: ANY_WITH_FUNCTION required_function: preferred_term: DNA-directed DNA polymerase activity term: id: GO:0003887 label: DNA-directed DNA polymerase activity gene_product: preferred_term: 2 (Bacillus phage phi29) term: id: UniProtKB:P03680 label: DNA polymerase description: 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: preferred_term: DNA-directed DNA polymerase activity term: id: GO:0003887 label: DNA-directed DNA polymerase activity processes: - preferred_term: viral DNA genome replication term: id: GO:0039693 label: viral DNA genome replication locations: - preferred_term: host cell cytoplasm term: id: GO:0030430 label: host cell cytoplasm role_description: Catalyzes protein-primed initiation and continuous strand-displacement replication of linear dsDNA genomes. knowledge_gaps: - gap_statement: Gene Ontology lacks specific biological process terms for phage-mediated sigma-factor appropriation (such as T4 AsiA + MotA remodeling of host sigma70) and sliding-clamp-coupled late promoter activation (T4 gp55-gp33-gp45). Biologically, dozens of early phage accessory genes located in anti-defense islands lack identified host immune targets across newly discovered bacterial defense families. boundary: Annotate these factors to GO:0019083 (viral transcription) and GO:0039653 (symbiont-mediated suppression of host transcription). gap_kind: - BIOLOGY - ONTOLOGY