Replication restart protein PriA

Function

Initiates the restart of stalled replication forks, which reloads the DnaB replicative helicase on sites other than the origin of replication. Recognizes abandoned replication forks and remodels them to uncover a loading site for DnaB. Serves as the scaffold for primosome assembly. There are several restart pathways, the PriA-PriB pathway is the major replication restart pathway. The PriA-PriB pathway is subdivided into 2 distinct pathways. The PriA-PriC pathway is a minor restart pathway. Recognizes and binds the arrested nascent DNA chain at stalled replication forks. Unwinds the lagging strand at DNA replication forks in the presence of DNA single-stranded binding protein (SSB). A 3'-5' DNA helicase that requires (d)ATP and is enhanced by DNA single-stranded binding protein (SSB) and/or PriB. Can remodel the DNA duplex, via its helicase activity, and promotes assembly of the primosome and loading of the major replicative helicase DnaB onto DNA. Helicase activity is not essential for primosome assembly in the PriA-PriB pathway, but is required for the PriA-PriC pathway. Binds to branched DNA structures that resemble D-loops, stalled replication forks or to the primosome assembly site (PAS) in some phage. Binds to DNA in two distinct modes, either dependent on or independent of, recognition of the 3' terminus. Crucial for homologous recombination and double-strand break repair. Required for growth even in the absence of DNA damage.

Classification

Family (Pfam)

PF00270 DEAD, PF00271 Helicase_C, PF17764 PriA_3primeBD, PF18074 PriA_C, PF21213 WHD_PriA, PF18319 Zn_ribbon_PriA

InterPro

DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd, Helicase_C-like, P-loop_NTPase, PriA, PriA_3primeBD, PriA_3primeBD_sf, PriA_C, PriA_CRR, WHD_PriA

Functional cluster

trans-Translation & rRNA Methyltransferases

Experimental structures · PDB · 8

• 2D7E X-ray 2.50A
• 2D7G X-ray 3.30A
• 2D7H X-ray 3.00A
• 2DWL X-ray 3.20A
• 2DWM X-ray 3.15A
• 2DWN X-ray 3.35A
• 6DCR X-ray 1.98A
• 8FAK EM 3.22A

A predicted model is available from AlphaFold.

Gene Ontology · 17

• GO:1990077 primosome complex
• GO:0043138 3'-5' DNA helicase activity
• GO:0005524 ATP binding
• GO:0016887 ATP hydrolysis activity
• GO:0003677 DNA binding
• GO:0004386 helicase activity
• GO:0008270 zinc ion binding
• GO:0006310 DNA recombination
• GO:0006260 DNA replication
• GO:0006270 DNA replication initiation
• GO:0006269 DNA replication, synthesis of primer
• GO:0006261 DNA-templated DNA replication
• GO:0006302 double-strand break repair
• GO:0006276 plasmid maintenance
• GO:0031297 replication fork processing
• GO:0046677 response to antibiotic
• GO:0010332 response to gamma radiation

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Replication restart protein PriA 0.98
• Replication restart protein PriA 0.89
• Replication restart protein PriA 0.79
• DNA polymerase III subunit delta' 0.69
• Ribosomal RNA small subunit methyltransferase B 0.68
• Ribosomal RNA small subunit methyltransferase B 0.68
• DNA polymerase III subunit delta' 0.68
• Ribosomal RNA small subunit methyltransferase B 0.68
• tRNA(Met) cytidine acetyltransferase TmcA 0.68
• tRNA(Met) cytidine acetyltransferase TmcA 0.68
• Ribosomal RNA small subunit methyltransferase B 0.67
• Ribosomal RNA small subunit methyltransferase B 0.67

Co-cited proteins · studied together in the literature

• Replication restart protein PriB 12 shared papers
• Replication restart protein PriA 2 shared papers
• Replication restart protein PriC 7 shared papers
• HTH-type transcriptional repressor CytR 1 shared papers
• Replication restart protein DnaT 5 shared papers
• ATP-dependent DNA helicase RecG 2 shared papers
• Replication restart protein PriA 1 shared papers
• Single-stranded DNA-binding protein 1 1 shared papers
• Replicative helicase loader DnaC 5 shared papers
• Single-stranded DNA-binding protein 1 shared papers
• ATP-dependent DNA helicase Rep 3 shared papers
• Replication restart protein PriA 1 shared papers

Literature · 44 cited papers

• Replication fork binding triggers structural changes in the PriA helicase that govern DNA replication restart in E. coli. Nat. Commun. · 2023
• Identification of genetic interactions with priB links the PriA/PriB DNA replication restart pathway to double-strand DNA break repair in Escherichia coli. G3 (Bethesda) · 2022
• Escherichia coli K-12 has two distinguishable PriA-PriB replication restart pathways. Mol. Microbiol. · 2021
• Resolving Toxic DNA repair intermediates in every E. coli replication cycle: critical roles for RecG, Uup and RadD. Nucleic Acids Res. · 2020
• Structure-specific DNA replication-fork recognition directs helicase and replication restart activities of the PriA helicase. Proc. Natl. Acad. Sci. U.S.A. · 2018
• Structural mechanisms of PriA-mediated DNA replication restart. Proc. Natl. Acad. Sci. U.S.A. · 2014
• The PriA replication restart protein blocks replicase access prior to helicase assembly and directs template specificity through its ATPase activity. J. Biol. Chem. · 2013
• Identification of a small molecule PriA helicase inhibitor. Biochemistry · 2012
• Cellular characterization of the primosome and rep helicase in processing and restoration of replication following arrest by UV-induced DNA damage in Escherichia coli. J. Bacteriol. · 2012
• Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia coli. Mol. Cell · 2009
• A hand-off mechanism for primosome assembly in replication restart. Mol. Cell · 2007
• Escherichia coli PriA protein, two modes of DNA binding and activation of ATP hydrolysis. J. Biol. Chem. · 2007
• … and 32 more in the literature graph