DNA replication

Kornberg, Arthur

doi:10.1016/0968-0004(84)90114-2

Cited by 415 publications

(629 citation statements)

References 15 publications

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“…The reproduction and evolution of life depends on the accurate replication of the genome, which is facilitated by DNA polymerases (Kornberg & Baker, 1992). The synthesis of new DNA molecules would be impossible without these enzymes as they increase the rate of phosphodiester bond formation by many orders of magnitude compared with the corresponding uncatalyzed reaction in water (Schroeder et al 2006 ;Wolfenden & Snider, 2001).…”

Section: Dna Polymerases and Replication Fidelity 431 Introductionmentioning

confidence: 99%

Why nature really chose phosphate

Kamerlin

Sharma

Prasad

et al. 2013

Quart. Rev. Biophys.

339

448

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Phosphoryl transfer plays key roles in signaling, energy transduction, protein synthesis, and maintaining the integrity of the genetic material. On the surface, it would appear to be a simple nucleophile displacement reaction. However, this simplicity is deceptive, as, even in aqueous solution, the low-lying d-orbitals on the phosphorus atom allow for eight distinct mechanistic possibilities, before even introducing the complexities of the enzyme catalyzed reactions. To further complicate matters, while powerful, traditional experimental techniques such as the use of linear free-energy relationships (LFER) or measuring isotope effects cannot make unique distinctions between different potential mechanisms. A quarter of a century has passed since Westheimer wrote his seminal review, ‘Why Nature Chose Phosphate’ (Science 235 (1987), 1173), and a lot has changed in the field since then. The present review revisits this biologically crucial issue, exploring both relevant enzymatic systems as well as the corresponding chemistry in aqueous solution, and demonstrating that the only way key questions in this field are likely to be resolved is through careful theoretical studies (which of course should be able to reproduce all relevant experimental data). Finally, we demonstrate that the reason that naturereallychose phosphate is due to interplay between two counteracting effects: on the one hand, phosphates are negatively charged and the resulting charge-charge repulsion with the attacking nucleophile contributes to the very high barrier for hydrolysis, making phosphate esters among the most inert compounds known. However, biology is not only about reducing the barrier to unfavorable chemical reactions. That is, the same charge-charge repulsion that makes phosphate ester hydrolysis so unfavorable also makes it possible to regulate, by exploiting the electrostatics. This means that phosphate ester hydrolysis can not only be turned on, but also be turned off, by fine tuning the electrostatic environment and the present review demonstrates numerous examples where this is the case. Without this capacity for regulation, it would be impossible to have for instance a signaling or metabolic cascade, where the action of each participant is determined by the fine-tuned activity of the previous piece in the production line. This makes phosphate esters the ideal compounds to facilitate life as we know it.

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Section: Dna Polymerases and Replication Fidelity 431 Introductionmentioning

confidence: 99%

Why nature really chose phosphate

Kamerlin

Sharma

Prasad

et al. 2013

Quart. Rev. Biophys.

339

448

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“…However, an additional 'connector' protein called binds two molecules of Pol III core and one complex to produce a tightly associated particle called Pol III* (Onrust et al 1995). The two Pol III core polymerases are thought to replicate the leading and lagging strands concurrently (Sinha 1980;Kornberg & Baker 1992).…”

Section: Introductionmentioning

confidence: 99%

Clamp loading, unloading and intrinsic stability of the PCNA, β and gp45 sliding clamps of human, E. coli and T4 replicases

et al. 1996

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Background: The high speed and processivity of replicative DNA polymerases reside in a processivity factor which has been shown to be a ring-shaped protein. This protein ('sliding clamp') encircles DNA and tethers the catalytic unit to the template. Although in eukaryotic, prokaryotic and bacteriophage-T4 systems, the processivity factors are ring-shaped, they assume different oligomeric states. The Escherichia coli clamp (the¯subunit) is active as a dimer while the eukaryotic and T4 phage clamps (PCNA and gp45, respectively) are active as trimers. The clamp can not assemble itself on DNA. Instead, a protein complex known as a clamp loader utilizes ATP to assemble the ring around the primer-template. This study compares properties of the human PCNA clamp with those of E. coli and T4 phage.

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“…They revealed Received 4 October, 1996;revised 18 December, 1996; accepted 3 January, 1997. Present addresses: tDFG, Kennedy Q 1997 Blackwell Science Ctd that Pol I is involved in replication and necessary for a large number of DNA-repair processes such as nucleotideexcision repair, post-replicative recombination repair and base-excision repair (Sharma and Smith, 1987;Savic et a/., 1990;Kornberg and Baker, 1992;Friedberg et a/., 1995). Furthermore, Pol I is essential for replication of some plasmids such as ColE1 (Staudenbauer, 1976).…”

Section: Introductionmentioning

confidence: 99%

DnaA protein stimulates polA gene expression in Escherichia coli

Quiñones

Wandt

Kleinstäuber

et al. 1997

Molecular Microbiology

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SummaryThe polA gene of Escherichia coli encodes DNA polymerase I that is involved in DNA replication and repair. Despite the wide knowledge about structure and function of DNA polymerase I, there is little insight into the regulatory mechanisms involved in polA expression. DnaA is the initiator protein for DNA replication in E. coli. There are two putative DnaA-binding sites within the extended promoter region of polA. In this work we studied the influence of altered levels of DnaA protein on polA expression. We found that DnaA overproduction increases polA expression in stationary-phase cultures. The stimulation effect was independent of rpoS, which encodes the sigma factor for stationary-phaseinducible genes. However, it was modulated by ppGpp. Comparative S1 analyses revealed that the induction was based on transcriptional stimulation. Footprinting experiments demonstrated that DnaA binds only to the proximal DnaA box near the polA promoter. These results suggest an additional role for DnaA as transcriptional activator of polA at least under certain physiological conditions.

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DNA replication

Cited by 415 publications

References 15 publications

Why nature really chose phosphate

Why nature really chose phosphate

Clamp loading, unloading and intrinsic stability of the PCNA, β and gp45 sliding clamps of human, E. coli and T4 replicases

DnaA protein stimulates polA gene expression in Escherichia coli

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