Limits...
Structural insight into the DNA-binding mode of the primosomal proteins PriA, PriB, and DnaT.

Huang YH, Huang CY - Biomed Res Int (2014)

Bottom Line: The assembly of the protein complexes within the forked DNA responsible for reloading the replicative DnaB helicase anywhere on the chromosome for genome duplication requires the coordination of transient biomolecular interactions.Over the last decade, investigations on the structure and mechanism of these nucleoproteins have provided considerable insight into primosome assembly.In this review, we summarize and discuss our current knowledge and recent advances on the DNA-binding mode of the primosomal proteins PriA, PriB, and DnaT.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung City 40201, Taiwan.

ABSTRACT
Replication restart primosome is a complex dynamic system that is essential for bacterial survival. This system uses various proteins to reinitiate chromosomal DNA replication to maintain genetic integrity after DNA damage. The replication restart primosome in Escherichia coli is composed of PriA helicase, PriB, PriC, DnaT, DnaC, DnaB helicase, and DnaG primase. The assembly of the protein complexes within the forked DNA responsible for reloading the replicative DnaB helicase anywhere on the chromosome for genome duplication requires the coordination of transient biomolecular interactions. Over the last decade, investigations on the structure and mechanism of these nucleoproteins have provided considerable insight into primosome assembly. In this review, we summarize and discuss our current knowledge and recent advances on the DNA-binding mode of the primosomal proteins PriA, PriB, and DnaT.

Show MeSH

Related in: MedlinePlus

A hand-off mechanism for the replication restart primosome assembly. The proposed assembly mechanism is as follows. (i) PriA recognizes and binds to a replication fork, (ii) PriB joins PriA to form a PriA-PriB-DNA ternary complex, (iii) DnaT participates in this nucleocomplex to form a triprotein complex, in which PriB is released from ssDNA due to recruitment of DnaT, (iv) the PriA-PriB-DnaT-DNA quaternary complex loads the DnaB/C complex, and (v) DnaB is loaded on the lagging strand template.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4129139&req=5

fig2: A hand-off mechanism for the replication restart primosome assembly. The proposed assembly mechanism is as follows. (i) PriA recognizes and binds to a replication fork, (ii) PriB joins PriA to form a PriA-PriB-DNA ternary complex, (iii) DnaT participates in this nucleocomplex to form a triprotein complex, in which PriB is released from ssDNA due to recruitment of DnaT, (iv) the PriA-PriB-DnaT-DNA quaternary complex loads the DnaB/C complex, and (v) DnaB is loaded on the lagging strand template.

Mentions: A hand-off mechanism for PriA-directed primosome assembly [15] has been proposed (Figure 2), whereby (i) PriA recognizes and binds to a replication fork; (ii) PriB joins PriA to form a PriA-PriB-DNA ternary complex; (iii) DnaT participates in this nucleocomplex to form a triprotein complex, in which PriB is released from ssDNA due to recruitment of DnaT; (iv) the PriA-PriB-DnaT-DNA quaternary complex loads the DnaB/C complex; (v) DnaB is loaded on the lagging strand template. Genetic analyses suggest that these primosomal proteins are essential replication proteins for bacterial cell growth [12, 16–21]. These proteins are required for reinitiating chromosomal DNA replication in bacteria; thus, blocking their activities would be detrimental to bacterial survival [22, 23]. Several primosomal proteins, such as PriA, PriB, PriC, and DnaT, are not found in humans; thus, these proteins may be potential targets in developing antibiotics for the six antibiotic-resistant pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.) [24, 25]. The recently discovered inhibitor CGS 15943 targets Neisseria gonorrhoeae PriA helicase with an IC50 of 114 ± 24 μM [26].


Structural insight into the DNA-binding mode of the primosomal proteins PriA, PriB, and DnaT.

Huang YH, Huang CY - Biomed Res Int (2014)

A hand-off mechanism for the replication restart primosome assembly. The proposed assembly mechanism is as follows. (i) PriA recognizes and binds to a replication fork, (ii) PriB joins PriA to form a PriA-PriB-DNA ternary complex, (iii) DnaT participates in this nucleocomplex to form a triprotein complex, in which PriB is released from ssDNA due to recruitment of DnaT, (iv) the PriA-PriB-DnaT-DNA quaternary complex loads the DnaB/C complex, and (v) DnaB is loaded on the lagging strand template.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129139&req=5

fig2: A hand-off mechanism for the replication restart primosome assembly. The proposed assembly mechanism is as follows. (i) PriA recognizes and binds to a replication fork, (ii) PriB joins PriA to form a PriA-PriB-DNA ternary complex, (iii) DnaT participates in this nucleocomplex to form a triprotein complex, in which PriB is released from ssDNA due to recruitment of DnaT, (iv) the PriA-PriB-DnaT-DNA quaternary complex loads the DnaB/C complex, and (v) DnaB is loaded on the lagging strand template.
Mentions: A hand-off mechanism for PriA-directed primosome assembly [15] has been proposed (Figure 2), whereby (i) PriA recognizes and binds to a replication fork; (ii) PriB joins PriA to form a PriA-PriB-DNA ternary complex; (iii) DnaT participates in this nucleocomplex to form a triprotein complex, in which PriB is released from ssDNA due to recruitment of DnaT; (iv) the PriA-PriB-DnaT-DNA quaternary complex loads the DnaB/C complex; (v) DnaB is loaded on the lagging strand template. Genetic analyses suggest that these primosomal proteins are essential replication proteins for bacterial cell growth [12, 16–21]. These proteins are required for reinitiating chromosomal DNA replication in bacteria; thus, blocking their activities would be detrimental to bacterial survival [22, 23]. Several primosomal proteins, such as PriA, PriB, PriC, and DnaT, are not found in humans; thus, these proteins may be potential targets in developing antibiotics for the six antibiotic-resistant pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp.) [24, 25]. The recently discovered inhibitor CGS 15943 targets Neisseria gonorrhoeae PriA helicase with an IC50 of 114 ± 24 μM [26].

Bottom Line: The assembly of the protein complexes within the forked DNA responsible for reloading the replicative DnaB helicase anywhere on the chromosome for genome duplication requires the coordination of transient biomolecular interactions.Over the last decade, investigations on the structure and mechanism of these nucleoproteins have provided considerable insight into primosome assembly.In this review, we summarize and discuss our current knowledge and recent advances on the DNA-binding mode of the primosomal proteins PriA, PriB, and DnaT.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences, Chung Shan Medical University, No. 110, Section 1, Chien-Kuo N. Road, Taichung City 40201, Taiwan.

ABSTRACT
Replication restart primosome is a complex dynamic system that is essential for bacterial survival. This system uses various proteins to reinitiate chromosomal DNA replication to maintain genetic integrity after DNA damage. The replication restart primosome in Escherichia coli is composed of PriA helicase, PriB, PriC, DnaT, DnaC, DnaB helicase, and DnaG primase. The assembly of the protein complexes within the forked DNA responsible for reloading the replicative DnaB helicase anywhere on the chromosome for genome duplication requires the coordination of transient biomolecular interactions. Over the last decade, investigations on the structure and mechanism of these nucleoproteins have provided considerable insight into primosome assembly. In this review, we summarize and discuss our current knowledge and recent advances on the DNA-binding mode of the primosomal proteins PriA, PriB, and DnaT.

Show MeSH
Related in: MedlinePlus