Mechanisms of bacterial DNA replication restart

Abstract Multi-protein DNA replication complexes called replisomes perform the essential process of copying cellular genetic information prior to cell division. Under ideal conditions, replisomes dissociate only after the entire genome has been duplicated. However, DNA replication rarely occurs without interruptions that can dislodge replisomes from DNA. Such events produce incompletely replicated chromosomes that, if left unrepaired, prevent the segregation of full genomes to daughter cells. To mitigate this threat, cells have evolved ‘DNA replication restart’ pathways that have been best defined in bacteria. Replication restart requires recognition and remodeling of abandoned replication forks by DNA replication restart proteins followed by reloading of the replicative DNA helicase, which subsequently directs assembly of the remaining replisome subunits. This review summarizes our current understanding of the mechanisms underlying replication restart and the proteins that drive the process in Escherichia coli (PriA, PriB, PriC and DnaT).

• Publication year

  2017

• Venue

  Nucleic Acids Research

• Publication date

  2017-11-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1093/nar/gkx1203PMID 29202195PMCID 5778457
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Reloading of the replicative DNA helicase directs assembly of the remaining replisome subunits.

  Confidence 0.88

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• PriA, PriB, PriC, and DnaT are the E. coli proteins emphasized as the key factors driving replication restart.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• Bacterial DNA replication restart proceeds through recognition and remodeling of abandoned replication forks before loading the replicative DNA helicase.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review

• abandoned replication forks

  DNA structure

  Replication fork structures that have been dislodged from DNA before chromosome duplication is complete.

  Aliases: abandoned forks, collapsed forks

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• dna replication restart

  process

  A bacterial pathway that reinitiates DNA replication after a replication fork has been disrupted or abandoned.

  Aliases: replication restart

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• dnat

  protein

  An E. coli replication restart protein that works with the restart machinery during helicase loading.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• escherichia coli

  species

  The bacterial species used as the main model for the restart mechanisms summarized in the review.

  Aliases: E. coli

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• pria

  protein

  An E. coli replication restart protein involved in recognizing restarted fork structures and initiating helicase loading.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• prib

  protein

  An E. coli replication restart protein that participates in the restart machinery.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• pric

  protein

  An E. coli replication restart protein that participates in the restart machinery.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• replicative dna helicase

  enzyme, protein

  The helicase enzyme that unwinds duplex DNA at the replication fork during chromosome duplication.

  Aliases: DNA helicase

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• replisome

  protein complex, complex

  The multi-protein DNA replication complex responsible for copying the genome.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review
• replisome subunits

  protein complex components, components

  The individual protein components that assemble into the DNA replication machinery.

  Aliases: remaining replisome subunits

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewAK (4715169a40) review

• Mechanisms of Post-Replication DNA Repair

  2017cited by this paper
• Staphylococcus aureus single-stranded DNA-binding protein SsbA can bind but cannot stimulate PriA helicase

  2017cited by this paper
• The essential kinase ATR: ensuring faithful duplication of a challenging genome

  2017cited by this paper
• Replication Fork Protection Factors Controlling R-Loop Bypass and Suppression

  2017cited by this paper
• Building up and breaking down: mechanisms controlling recombination during replication

  2017cited by this paper
• A priA Mutant Expressed in Two Pieces Has Almost Full Activity in Escherichia coli K-12

  2017cited by this paper
• Frequent exchange of the DNA polymerase during bacterial chromosome replication

  2017cited by this paper
• Structural analyses of the bacterial primosomal protein DnaB reveal that it is a tetramer and forms a complex with a primosomal re-initiation protein

  2017cited by this paper
• The impact of replication stress on replication dynamics and DNA damage in vertebrate cells

  2017cited by this paper
• Transcription leads to pervasive replisome instability in bacteria

  2017cited by this paper
• Replication Restart in Bacteria

  2017cited by this paper
• Frequent exchange of the DNA polymerase during bacterial chromosome replication

  2017cited by this paper
• Mechanisms for initiating cellular DNA replication

  2017cited by this paper
• DnaT is a PriC-binding protein.

  2016cited by this paper
• Conflict Resolution in the Genome: How Transcription and Replication Make It Work.

  2016cited by this paper
• Fork restart protein, PriA, binds around oriC after depletion of nucleotide precursors: Replication fork arrest near the replication origin.

  2016cited by this paper
• SSB binds to the RecG and PriA helicases in vivo in the absence of DNA

  2016cited by this paper
• An aromatic-rich loop couples DNA binding and ATP hydrolysis in the PriA DNA helicase

  2016cited by this paper
• RecG Directs DNA Synthesis during Double-Strand Break Repair

  2016cited by this paper
• Replication stress: getting back on track

  2016cited by this paper
• Characterization of Staphylococcus aureus Primosomal DnaD Protein: Highly Conserved C-Terminal Region Is Crucial for ssDNA and PriA Helicase Binding but Not for DnaA Protein-Binding and Self-Tetramerization

  2016influential reference
• Structure and Function of the PriC DNA Replication Restart Protein*

  2016influential reference
• Bacterial and Eukaryotic Replisome Machines.

  2016cited by this paper
• Identification of Subunit Binding Positions on a Model Fork and Displacements That Occur during Sequential Assembly of the Escherichia coli Primosome*

  2015influential reference
• HLTF's Ancient HIRAN Domain Binds 3' DNA Ends to Drive Replication Fork Reversal.

  2015cited by this paper
• Structure of a Novel DNA-binding Domain of Helicase-like Transcription Factor (HLTF) and Its Functional Implication in DNA Damage Tolerance*

  2015cited by this paper
• CRISPR adaptation biases explain preference for acquisition of foreign DNA

  2015cited by this paper
• Deinococcus radiodurans PriA is a Pseudohelicase

  2015influential reference
• Are the SSB-Interacting Proteins RecO, RecG, PriA and the DnaB-Interacting Protein Rep Bound to Progressing Replication Forks in Escherichia coli?

  2015cited by this paper
• Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling

  2015cited by this paper
• Basic and aromatic residues in the C-terminal domain of PriC are involved in ssDNA and SSB binding.

  2015cited by this paper
• Different genome stability proteins underpin primed and naïve adaptation in E. coli CRISPR-Cas immunity

  2015cited by this paper
• Replication Restart after Replication-Transcription Conflicts Requires RecA in Bacillus subtilis

  2015cited by this paper
• DnaC traps DnaB as an open ring and remodels the domain that binds primase

  2015cited by this paper
• Crystal structure of DnaT84–153-dT10 ssDNA complex reveals a novel single-stranded DNA binding mode

  2014cited by this paper
• Involvement of histidine in complex formation of PriB and single-stranded DNA.

  2014cited by this paper
• Loading strategies of ring-shaped nucleic acid translocases and helicases.

  2014cited by this paper
• Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources.

  2014cited by this paper
• Structure and mechanism of the primosome protein DnaT– functional structures for homotrimerization, dissociation of ssDNA from the PriB·ssDNA complex, and formation of the DnaT·ssDNA complex

  2014influential reference
• DnaT is a single‐stranded DNA binding protein

  2013cited by this paper
• Rescuing stalled or damaged replication forks.

  2013cited by this paper
• Avoiding chromosome pathology when replication forks collide

  2013cited by this paper
• Protein–DNA complexes are the primary sources of replication fork pausing in Escherichia coli

  2013cited by this paper
• Structural mechanisms of PriA-mediated DNA replication restart

  2013influential reference
• The bacterial DnaC helicase loader is a DnaB ring breaker.

  2013cited by this paper
• Transcription-replication encounters, consequences and genomic instability

  2013cited by this paper
• Mechanisms for initiating cellular DNA replication.

  2013cited by this paper
• The Escherichia coli primosomal DnaT protein exists in solution as a monomer-trimer equilibrium system.

  2013cited by this paper
• The N-terminal domain of DnaT, a primosomal DNA replication protein, is crucial for PriB binding and self-trimerization.

  2013cited by this paper
• Energetics of the Escherichia coli DnaT protein trimerization reaction.

  2013cited by this paper
• Yeast Two-Hybrid Analysis of PriB-Interacting Proteins in Replication Restart Primosome: A Proposed PriB–SSB Interaction Model

  2013cited by this paper
• PriC-mediated DNA Replication Restart Requires PriC Complex Formation with the Single-stranded DNA-binding Protein*

  2013cited by this paper
• Domain separation and characterization of PriC, a replication restart primosome factor in Escherichia coli

  2013influential reference
• Solution structure of the N‐terminal domain of a replication restart primosome factor, PriC, in Escherichia coli

  2013influential reference
• Crystal structure and DNA‐binding mode of Klebsiella pneumoniae primosomal PriB protein

  2012cited by this paper
• Replication–transcription conflicts in bacteria

  2012cited by this paper
• Identification of a small molecule PriA helicase inhibitor.

  2012cited by this paper
• Modulation of DNA damage tolerance in Escherichia coli recG and ruv strains by mutations affecting PriB, the ribosome and RNA polymerase

  2012cited by this paper
• Replication Fork Reversal after Replication–Transcription Collision

  2012cited by this paper
• Cellular Characterization of the Primosome and Rep Helicase in Processing and Restoration of Replication following Arrest by UV-Induced DNA Damage in Escherichia coli

  2012cited by this paper
• The PriA Replication Restart Protein Blocks Replicase Access Prior to Helicase Assembly and Directs Template Specificity through Its ATPase Activity*

  2012influential reference
• Binding of two PriA-PriB complexes to the primosome assembly site initiates primosome formation.

  2011influential reference
• Transcription termination maintains chromosome integrity

  2010cited by this paper
• Interaction of Rep and DnaB on DNA

  2010cited by this paper
• The Escherichia coli PriA helicase-double-stranded DNA complex: location of the strong DNA-binding subsite on the helicase domain of the protein and the affinity control by the two nucleotide-binding sites of the enzyme.

  2010cited by this paper
• Co-directional replication-transcription conflicts lead to replication restart

  2010cited by this paper
• The Escherichia coli PriA Helicase Specifically Recognizes Gapped DNA Substrates

  2010cited by this paper
• Interactions of the Escherichia coli primosomal PriB protein with the single-stranded DNA. Stoichiometries, intrinsic affinities, cooperativities, and base specificities.

  2010cited by this paper
• Rep Provides a Second Motor at the Replisome to Promote Duplication of Protein-Bound DNA

  2009cited by this paper
• The crystal structure of Neisseria gonorrhoeae PriB reveals mechanistic differences among bacterial DNA replication restart pathways

  2009cited by this paper
• Strand Displacement by DNA Polymerase III Occurs through a τ-ψ-χ Link to Single-stranded DNA-binding Protein Coating the Lagging Strand Template*

  2009cited by this paper
• The helicases DinG, Rep and UvrD cooperate to promote replication across transcription units in vivo

  2009cited by this paper
• The replication fork trap and termination of chromosome replication

  2008cited by this paper
• SbcCD causes a double-strand break at a DNA palindrome in the Escherichia coli chromosome.

  2008cited by this paper
• DNA Damage Differentially Activates Regional Chromosomal Loci for Tn7 Transposition in Escherichia coli

  2008cited by this paper
• Non-replicative helicases at the replication fork.

  2007cited by this paper
• Structural basis of the 3′‐end recognition of a leading strand in stalled replication forks by PriA

  2007cited by this paper
• A hand-off mechanism for primosome assembly in replication restart.

  2007influential reference
• Structure and mechanism of helicases and nucleic acid translocases.

  2007cited by this paper
• Escherichia coli PriA Protein, Two Modes of DNA Binding and Activation of ATP Hydrolysis*

  2007cited by this paper
• Mutational analysis reveals Escherichia coli oriC interacts with both DnaA‐ATP and DnaA‐ADP during pre‐RC assembly

  2007cited by this paper
• Anticipating chromosomal replication fork arrest: SSB targets repair DNA helicases to active forks

  2007cited by this paper
• Crystallization and preliminary crystallographic analysis of the N-terminal domain of PriA from Escherichia coli.

  2006cited by this paper
• Roles of PriA Protein and Double-Strand DNA Break Repair Functions in UV-Induced Restriction Alleviation in Escherichia coli

  2006cited by this paper
• Allosteric interactions between the nucleotide-binding sites and the ssDNA-binding site in the PriA helicase-ssDNA complex. 3.

  2006cited by this paper
• Complexed crystal structure of replication restart primosome protein PriB reveals a novel single-stranded DNA-binding mode

  2006cited by this paper
• A novel dnaC mutation that suppresses priB rep mutant phenotypes in Escherichia coli K‐12

  2006influential reference
• Kinetic mechanisms of the nucleotide cofactor binding to the strong and weak nucleotide-binding site of the Escherichia coli PriA helicase. 2.

  2006cited by this paper
• The Escherichia coli PriA helicase has two nucleotide-binding sites differing dramatically in their affinities for nucleotide cofactors. 1. Intrinsic affinities, cooperativities, and base specificity of nucleotide cofactor binding.

  2006cited by this paper
• Stabilization of a Stalled Replication Fork by Concerted Actions of Two Helicases*

  2006cited by this paper
• PriB Stimulates PriA Helicase via an Interaction with Single-stranded DNA*

  2005influential reference
• Interaction network containing conserved and essential protein complexes in Escherichia coli

  2005cited by this paper
• Requirements for Replication Restart Proteins During Constitutive Stable DNA Replication in Escherichia coli K-12

  2005cited by this paper
• Crystal structure of a biologically functional form of PriB from Escherichia coli reveals a potential single-stranded DNA-binding site.

  2005cited by this paper
• The disposition of nascent strands at stalled replication forks dictates the pathway of replisome loading during restart.

  2005influential reference
• Mutation of the priA Gene of Neisseria gonorrhoeae Affects DNA Transformation and DNA Repair

  2005cited by this paper
• Unwinding of the Nascent Lagging Strand by Rep and PriA Enables the Direct Restart of Stalled Replication Forks*[boxs]

  2005influential reference
• Replication Termination in Escherichia coli: Structure and Antihelicase Activity of the Tus-Ter Complex

  2005cited by this paper
• Cisplatin induces DNA double-strand break formation in Escherichia coli dam mutants.

  2005cited by this paper
• Allele specific synthetic lethality between priC and dnaAts alleles at the permissive temperature of 30°C in E. coli K-12

  2004cited by this paper

• Termination of DNA replication drives genomic instability via multiple mechanisms

  2026cites this paper
• Visualization of the complete primosome reveals the structural mechanisms governing DNA replication restart

  2026cites this paper
• Antiplasmid systems: a novel strategy to combat antibiotic resistance.

  2025cites this paper
• Hallmarks of DNA replication stress responses in Escherichia coli and Bacillus subtilis

  2025cites this paper
• Saccharin disrupts bacterial cell envelope stability and interferes with DNA replication dynamics

  2025cites this paper
• Mechanism of Annealing of Complementary DNA Strands by the Single-Stranded DNA Binding Protein of Bacteriophage T7.

  2025cites this paper
• Subunit Communication within Dimeric SF1 DNA Helicases

  2024cites this paper
• The intrinsically disordered linker in the single-stranded DNA-binding protein influences DNA replication restart and recombination pathways in Escherichia coli K-12

  2024cites this paper
• Dysregulated DnaB unwinding induces replisome decoupling and daughter strand gaps that are countered by RecA polymerization

  2024cites this paper
• Molecular insights into the prototypical single-stranded DNA-binding protein from E. coli

  2024cites this paper
• Frequent nonhomologous replacement of replicative helicase loaders by viruses in Vibrionaceae

  2024cites this paper
• Biochemical characterization of Escherichia coli DnaC variants that alter DnaB helicase loading onto DNA

  2024cites this paper
• Resolving the polycistronic aftermath: Essential role of topoisomerase IA in preventing R-loops in Leishmania

  2024cites this paper
• Replication fork binding triggers structural changes in the PriA helicase that govern DNA replication restart in E. coli

  2023cites this paper
• Crystal Structure of DNA Replication Protein SsbA Complexed with the Anticancer Drug 5-Fluorouracil

  2023cites this paper
• SMC-based immunity against extrachromosomal DNA elements

  2023cites this paper
• Oligomeric state of the N-terminal domain of DnaT for replication restart in Escherichia coli.

  2023cites this paper
• Inhibition of Replication Fork Formation and Progression: Targeting the Replication Initiation and Primosomal Proteins

  2023cites this paper
• Bacillus subtilis RadA/Sms-Mediated Nascent Lagging-Strand Unwinding at Stalled or Reversed Forks Is a Two-Step Process: RadA/Sms Assists RecA Nucleation, and RecA Loads RadA/Sms

  2023influential citation
• The Bacillus subtilis PriA Winged Helix Domain Is Critical for Surviving DNA Damage

  2022cites this paper
• The Caulobacter crescentus DciA promotes chromosome replication through topological loading of the DnaB replicative helicase at replication forks

  2022cites this paper
• Use of an unnatural amino acid to map helicase/DNA interfaces via photoactivated crosslinking.

  2022cites this paper
• Identification of genetic interactions with priB links the PriA/PriB DNA replication restart pathway to double-strand DNA break repair in Escherichia coli

  2022cites this paper
• TT-pocket/HIRAN: binding to 3'-terminus of DNA for recognition and processing of stalled replication forks.

  2022cites this paper
• Role for DNA double strand end-resection activity of RecBCD in control of aberrant chromosomal replication initiation in Escherichia coli

  2022cites this paper
• The Putative Endonuclease Activity of MutL Is Required for the Segmental Gene Conversion Events That Drive Antigenic Variation of the Lyme Disease Spirochete

  2022cites this paper
• A Complexed Crystal Structure of a Single-Stranded DNA-Binding Protein with Quercetin and the Structural Basis of Flavonol Inhibition Specificity

  2022cites this paper
• Single-molecule binding characterization of primosomal protein PriA involved in replication restart.

  2021cites this paper
• Characterize the Interaction of the DNA Helicase PriA with the Stalled DNA Replication Fork Using Atomic Force Microscopy.

  2021cites this paper
• Comparing SSB-PriA Functional and Physical Interactions in Gram-Positive and -Negative Bacteria.

  2021cites this paper
• Dynamics of the PriA Helicase at Stalled DNA Replication Forks.

  2021cites this paper
• Beneficial and detrimental genes in the cellular response to replication arrest

  2021cites this paper
• Regulation of E. coli Rep Helicase Activity by PriC.

  2021cites this paper
• DnaB helicase dynamics in bacterial DNA replication resolved by single-molecule studies

  2021cites this paper
• Examination of the roles of a conserved motif in the PriA helicase in structure-specific DNA unwinding and processivity

  2021cites this paper
• Escherichia coli K‐12 has two distinguishable PriA‐PriB replication restart pathways

  2021cites this paper
• Single-molecule studies of helicases and translocases in prokaryotic genome-maintenance pathways.

  2021cites this paper
• RecA and RecB: probing complexes of DNA repair proteins with mitomycin C in live Escherichia coli with single-molecule sensitivity

  2021cites this paper
• Characterization of the Chimeric PriB-SSBc Protein

  2021cites this paper
• Evaluating Scalable Supervised Learning for Synthesize-on-Demand Chemical Libraries

  2021cites this paper
• Atomic force microscopy–based characterization of the interaction of PriA helicase with stalled DNA replication forks

  2020cites this paper
• Mechanisms of Theta Plasmid Replication in Enterobacteria and Implications for Adaptation to Its Host

  2020cites this paper
• AFM characterization of the interaction of PriA helicase with stalled DNA replication forks

  2020cites this paper
• Mutational Analysis of Residues in PriA and PriC Affecting Their Ability To Interact with SSB in Escherichia coli K-12

  2020cites this paper
• Double strand break (DSB) repair in Cyanobacteria: Understanding the process in an ancient organism.

  2020cites this paper
• A structural model of the PriB–DnaT complex in Escherichia coli replication restart

  2020cites this paper
• Resolving Toxic DNA repair intermediates in every E. coli replication cycle: critical roles for RecG, Uup and RadD

  2020cites this paper
• Catalytically inactive T7 DNA polymerase imposes a lethal replication roadblock

  2020cites this paper
• Screening the antimicrobial effect of ferrocene-boronic acid on Pseudomonas aeruginosa using proteomics and metabolomics approach

  2020cites this paper
• Research Online Research Online Resolving Toxic DNA repair intermediates in every E. coli replication cycle: Resolving Toxic DNA repair intermediates in every E. coli replication cycle: critical roles for RecG, Uup and RadD critical roles for RecG, Uup and RadD

  2020cites this paper
• Too Much of a Good Thing: How Ectopic DNA Replication Affects Bacterial Replication Dynamics

  2020cites this paper
• A new role for Escherichia coli Dam DNA methylase in prevention of aberrant chromosomal replication

  2019cites this paper
• A structural view of bacterial DNA replication

  2019cites this paper
• Crystal structure of the C-terminal domain of the primosomal DnaT protein: Insights into a new oligomerization mechanism.

  2019cites this paper
• Characterization of an SSB–dT25 complex: structural insights into the S-shaped ssDNA binding conformation

  2019cites this paper
• Molecular and functional characterization of the Listeria monocytogenes RecA protein: insights into the homologous recombination process.

  2019cites this paper
• Complexed crystal structure of SSB reveals a novel single-stranded DNA binding mode (SSB)3:1: Phe60 is not crucial for defining binding paths.

  2019cites this paper
• DNA replication and replication termination in Escherichia coli

  2019influential citation
• Replisome structure suggests mechanism for continuous fork progression and post-replication repair.

  2019cites this paper
• Emergence of plasmid stability under non-selective conditions maintains antibiotic resistance

  2019cites this paper
• Bacterial Primosome

  2019cites this paper
• Bacillus subtilis RarA acts at the interplay between replication and repair-by-recombination.

  2019cites this paper
• Structure-specific DNA replication-fork recognition directs helicase and replication restart activities of the PriA helicase

  2018influential citation
• Replication Fork Breakage and Restart in Escherichia coli

  2018cites this paper
• The glycine-rich flexible region in SSB is crucial for PriA stimulation

  2018cites this paper
• The unstructured linker arms of MutL enable GATC site incision beyond roadblocks during initiation of DNA mismatch repair

  2018cites this paper
• Single-molecule live cell imaging of Rep reveals the dynamic interplay between an accessory replicative helicase and the replisome

  2018cites this paper
• SAAV2152 is a single-stranded DNA binding protein: the third SSB in Staphylococcus aureus

  2018cites this paper
• Characterization of single-stranded DNA-binding protein SsbB from Staphylococcus aureus: SsbB cannot stimulate PriA helicase

  2018cites this paper
• Function of a strand-separation pin element in the PriA DNA replication restart helicase

  2018influential citation
• Chromosomal over-replication in Escherichia coli recG cells is triggered by replication fork fusion and amplified if replichore symmetry is disturbed

  2018cites this paper