A novel role for site-specific recombination in maintenance of bacterial replicons

Austin, Stuart; Ziese, Marcia; Sternberg, Nat

doi:10.1016/0092-8674(81)90180-x

Cited by 305 publications

(160 citation statements)

References 19 publications

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“…Such plasmid prophages require some special mechanisms to ensure the stable inheritance in their lysogens. The circularized 93-kb genome of phage P1, the most extensively characterized among such phages (31), is stably maintained as a low-copy plasmid by multiple mechanisms: partitioning of the plasmid into daughter cells by the ParAB system, multimer resolution by the Cre-lox system, and postsegregational killing by the Phd-Doc toxin-antitoxin system (32)(33)(34). The c-st phage also encodes a XerC͞D family protein that probably resolves the plasmid multimer (35) and ParB-and FtsK͞SpoIIIE-like proteins that may be involved in plasmid partitioning or segregation (36,37).…”

Section: Discussionmentioning

confidence: 99%

The genome sequence ofClostridium botulinumtype C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny

Sakaguchi

Hayashi

Kurokawa

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

134

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Section: Discussionmentioning

confidence: 99%

The genome sequence ofClostridium botulinumtype C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny

Sakaguchi

Hayashi

Kurokawa

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

134

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“…In another approach, a cancer-specific promoter controls the expression of Cre site-specific recombinase [50], which activates the reporter or therapeutic gene expression in a second step (Figure 2b). The desired transgene is linked to a strong constitutive promoter that is interrupted by expression termination sequences flanked by two loxP sites, the cognate site of Cre.…”

Section: Augmenting Cancer-specific Expressionmentioning

confidence: 99%

“…Optimal TSTA constructs displayed activity levels significantly higher than those of the CMV promoter, while maintaining prostate cell specificity and androgen responsiveness [44,45]. In another approach, a cancer-specific promoter controls the expression of Cre site-specific recombinase [50], which activates the reporter or therapeutic gene expression in a second step (Figure 2b). The desired transgene is linked to a strong constitutive promoter that is interrupted by expression termination sequences flanked by two loxP sites, the cognate site of Cre.…”

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confidence: 99%

Transcriptionally targeted gene therapy to detect and treat cancer

Wu¹,

Johnson²,

Sato³

2003

Trends in Molecular Medicine

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The greatest challenge in cancer treatment is to achieve the highest levels of specificity and efficacy. Cancer gene therapy could be designed specifically to express therapeutic genes to induce cancer cell destruction. Cancer-specific promoters are useful tools to accomplish targeted expression; however, high levels of gene expression are needed to achieve therapeutic efficacy. Incorporating an imaging reporter gene in tandem with the therapeutic gene will allow tangible proof of principle that gene expression occurs at the correct location and at a sufficient level. Gene-based imaging can advance cancer detection and diagnosis. By combining the cancer-targeted imaging and therapeutic strategies, the exciting prospect of a 'one-two punch' to find hidden, disseminated cancer cells and destroy them simultaneously can potentially be realized.Multiple genetic alterations that confer growth advantages to tumor cells are accumulated during the transformation from normal to neoplastic growth [1]. The loss of growth suppressive genes or gain of oncogenes constitutes a common mechanism of oncogenesis. Based on this information, a rational therapeutic approach is to re-introduce the defective growth control genes into tumor cells. In addition, approaches of inducing apoptotic responses and enhancing anti-tumor immune responses have also been employed [2]. Due to the availability of multiple flexible therapeutic strategies, gene therapy is being actively investigated in clinical settings.Among the ~ 40 ongoing gene therapy clinical trials for cancer (searched via www.clinicaltrials.gov/), 18 of the trial protocols involve an immune activating scheme, ten studies employ a genetic correction strategy and five use a cytotoxic gene. With regard to genetic correction strategies, p53 is a major target. The recombinant adenovirus is the dominant viral gene delivery vector, and it is employed in 18 protocols. However, none of 40 protocols use a cancer-specific gene expression strategy. An oncolytic adenovirus CN706 containing prostate-specific antigen (PSA) promoter driven viral replication [3] is being evaluated in phase II clinical trial for prostate cancer [4].Because the goal of cancer gene therapy is to eradicate cancer cells, many therapeutic genes could be detrimental if unintentionally expressed in normal cells. Selectively targeting the cancer cells is useful to achieve safety and efficacy, especially when the gene therapy vector is directly delivered into patients. Based on features that distinguish cancerous from normal cells, three targeting strategies could be employed. Transcriptional targeting takes advantage of the fact that some cancer cells express a subset of exclusive genes, and uses these cancerspecific promoters to express the desired transgenes [5]. Transductional targeting refers to surface modification on the gene delivery vehicle to enhance interactions with the cancer cell membrane antigen, thereby improving gene transfer into the cancerous cell. A third promising approach is to exploit cancer-a...

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“…PCC 7120 through a genetic system based on cre-loxP (28). We demonstrate that PII from Synechocystis sp.…”

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confidence: 98%

PII Is Important in Regulation of Nitrogen Metabolism but Not Required for Heterocyst Formation in the Cyanobacterium Anabaena sp. PCC 7120

Zhang

Wang

et al. 2007

Journal of Biological Chemistry

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PII is an important signal protein for regulation of nitrogen metabolism in bacteria and plants. We constructed a mutant of glnB, encoding PII, in a heterocystous cyanobacterium, Anabaena sp. PCC 7120, with a cre-loxP system. The mutant (MP2␣) grew more slowly than the wild type under all nitrogen regimens. It excreted a large amount of ammonium when grown on nitrate due to altered activities of glutamine synthetase and nitrate reductase. MP2␣ had a low nitrogenase activity but was able to form heterocysts under diazotrophic conditions, suggesting that PII is not required for heterocyst differentiation. Analysis of the PII with mass spectroscopy found tyrosine nitration at Tyr-51 under diazotrophic conditions while no phosphorylation at Ser-49 was detected. The strains 51F and 49A, which have PII with mutations of Y51F and S49A, respectively, were constructed to analyze the functions of the two key residues on the T-loop. Like MP2␣, they had low nitrogenase activity and grew slowly under diazotrophic conditions. 49A was also impaired in nitrate uptake and formed heterocysts in the presence of nitrate. The up-regulation of ntcA after nitrogen stepdown, which was present in the wild type, was not observed in 51F and 49A. While our results showed that the Ser-49 residue is important to the function of PII in Anabaena sp. PCC 7120, evidence from the PII pattern of the wild type and 49A in nondenaturing gel electrophoresis suggested that Ser-49 is not modified. The possible physiological roles of tyrosine nitration of PII are discussed.

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A novel role for site-specific recombination in maintenance of bacterial replicons

Cited by 305 publications

References 19 publications

The genome sequence ofClostridium botulinumtype C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny

The genome sequence ofClostridium botulinumtype C neurotoxin-converting phage and the molecular mechanisms of unstable lysogeny

Transcriptionally targeted gene therapy to detect and treat cancer

PII Is Important in Regulation of Nitrogen Metabolism but Not Required for Heterocyst Formation in the Cyanobacterium Anabaena sp. PCC 7120

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