T4 Phage Replisome

Nelson, Scott W.; Zhuang, Zhihao; Spiering, Michelle M.; Benkovic, Stephen J.

doi:10.1007/b135974_16

Cited by 6 publications

(5 citation statements)

References 99 publications

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“…There are eight proteins which form the T4 DNA replisome these being DNA polymerase (gp43), clamp loaders (gp44, gp62, and gp45), single strand DNA binding protein (gp32), primase (gp61), helicase (gp41), and loading protein (gp59) (Nelson et al, 2009). CBB was found to have homologs to five of the eight proteins (CBB_263, 332, 277, 290, and 291), but lacks the clamp loaders (gp62, gp45) and loading protein (gp59).…”

Section: Resultsmentioning

confidence: 99%

Things Are Getting Hairy: Enterobacteria Bacteriophage vB_PcaM_CBB

et al. 2017

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Enterobacteria phage vB_PcaM_CBB is a “jumbo” phage belonging to the family Myoviridae. It possesses highly atypical whisker-like structures along the length of its contractile tail. It has a broad host range with the capability of infecting species of the genera Erwinia, Pectobacterium, and Cronobacter. With a genome of 355,922 bp, excluding a predicted terminal repeat of 22,456 bp, phage CBB is the third largest phage sequenced to date. Its genome was predicted to encode 554 ORFs with 33 tRNAs. Based on prediction and proteome analysis of the virions, 29% of its predicted ORFs could be functionally assigned. Protein comparison shows that CBB shares between 33–38% of its proteins with Cronobacter phage GAP32, coliphages PBECO4 and 121Q as well as Klebsiella phage vB_KleM_Rak2. This work presents a detailed and comparative analysis of vB_PcaM_CBB of a highly atypical jumbo myoviridae phage, contributing to a better understanding of phage diversity and biology.

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Section: Resultsmentioning

confidence: 99%

Things Are Getting Hairy: Enterobacteria Bacteriophage vB_PcaM_CBB

et al. 2017

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“…Despite the variation in number and nature of individual proteins between replication systems, the components that constitute an operative replication fork are faithfully represented in other more complex replication systems2. Therefore, what has been learned from the T4 replisome can be extended to the replisomes of other organisms, including higher eukaryotes3.…”

Section: Introductionmentioning

confidence: 99%

Response of the Bacteriophage T4 Replisome to Noncoding Lesions and Regression of a Stalled Replication Fork

Nelson

Benkovic

2010

Journal of Molecular Biology

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DNA is constantly damaged by endogenous and exogenous agents. The resulting DNA lesions have the potential to halt the progression of the replisome, possibly leading to replication fork collapse. Here, we examine the effect of a non-coding DNA lesion in either the leading or lagging strand template on the bacteriophage T4 replisome. A damaged base in the lagging strand template does not affect the progression of the replication fork. Instead, the stalled lagging strand polymerase recycles from the lesion and initiates synthesis of the new Okazaki fragment upstream from the damaged base. In contrast, when the replisome encounters a blocking lesion in the leading strand template, the replication fork only travels approximately 1 kb beyond the point of the DNA lesion before complete replication fork collapse. The primosome and lagging strand polymerase remain active during this period and an Okazaki fragment is synthesized beyond the point of the leading strand lesion. There is no evidence for a new priming event on the leading strand template. Instead, the DNA structure that is produced by the stalled replication fork is a substrate for the DNA repair helicase, UvsW. UvsW catalyzes the regression of a stalled replication fork into a "chicken foot" structure that has been postulated to be an intermediate in an error-free lesion bypass pathway.

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“…Additionally, many of the identified compounds resemble DNA mimics or nucleotide analogs and are likely non-specific inhibitors of nucleic-acid polymerases and enzymes that bind nucleic acids. To identify compounds that specifically inhibit P. falciparum apPOL, we screened the 979 potential inhibitors against bacteriophage T4 DNA polymerase 19 . T4 DNA polymerase can be produced in large quantities, and is in the same family (B-family) as the replicative human DNA polymerases (α, δ, and ε) 20 .…”

Section: Resultsmentioning

confidence: 99%

Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase

Kaur

Nieto

McDonald

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Malaria is caused by infection with protozoan parasites of the Plasmodium genus, which is part of the phylum Apicomplexa. Most organisms in this phylum contain a relic plastid called the apicoplast. The apicoplast genome is replicated by a single DNA polymerase (apPOL), which is an attractive target for anti-malarial drugs. We screened small-molecule libraries (206,504 compounds) using a fluorescence-based high-throughput DNA polymerase assay. Dose/response analysis and counter-screening identified 186 specific apPOL inhibitors. Toxicity screening against human HepaRG human cells removed 84 compounds and the remaining were subjected to parasite killing assays using chloroquine resistant P. falciparum parasites. Nine compounds were potent inhibitors of parasite growth and may serve as lead compounds in efforts to discover novel malaria drugs.

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T4 Phage Replisome

Cited by 6 publications

References 99 publications

Things Are Getting Hairy: Enterobacteria Bacteriophage vB_PcaM_CBB

Things Are Getting Hairy: Enterobacteria Bacteriophage vB_PcaM_CBB

Response of the Bacteriophage T4 Replisome to Noncoding Lesions and Regression of a Stalled Replication Fork

Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase

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