Mutations affecting sensitivity of the cellular slime mold Dictyostelium discoideum to DNA-damaging agents

Bronner, Christian; Welker, Dennis L.; Deering, R. A.

doi:10.1016/0921-8777(92)90065-b

Cited by 20 publications

(10 citation statements)

References 20 publications

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“…In Dictyostelium, at least eight non-allelic mutants that were isolated based on increased sensitivity to γ-irradiation also showed increased sensitivities to other DNA-damaging drugs (Bronner et al, 1992 ;Podgorski & Deering, 1980). The results of our mutant selection clearly illustrate that multiple genes and pathways are involved in the response to cisplatin.…”

Section: Discussionmentioning

confidence: 78%

“…Earlier work on Dictyostelium mutants which were isolated based on their sensitivity to γ-irradiation revealed that they were often sensitive to DNA-damaging chemicals as well (Bronner et al, 1992 & Deering, 1980). Therefore, we wished to determine if the cisplatin-resistant mutants we identified showed any cross-resistance to other DNA-damaging agents.…”

Section: Mutant Cells Are Specifically Resistant To Cisplatinmentioning

confidence: 99%

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Molecular basis for resistance to the anticancer drug cisplatin in Dictyostelium The GenBank accession numbers for the sequences reported in this paper are AF233610 (S-1-P lyase), AF233612 (PIP5K), AF233611 (P2Y purine receptor 1), AF233613 (CAAX prenyl protease) and AF233614 (unidentified gene).

Alexander

Schneider

et al. 2000

Microbiology

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The efficacy of the widely used chemotherapeutic drug cisplatin is limited by the occurrence of drug-resistant tumour cells. To fully exploit the potential of this drug in cancer therapy, it is imperative to understand the molecular basis of cisplatin resistance. Using an insertional mutagenesis technique in cells of Dictyostelium discoideum, we have identified six genes which are involved in cisplatin resistance. None of these genes has been previously linked to resistance to this drug. Several of these genes encode proteins that are involved in signal transduction pathways which regulate cell death, cell proliferation or gene regulation. The resistance of these mutant strains is specific for cisplatin, since deletion of these genes does not confer resistance to other DNA-damaging agents. Significantly, the disruption of three of these genes, encoding the sphingosine-1-phosphate lyase, the RegA cAMP phosphodiesterase and a phosphatidylinositol-4-phosphate 5-kinase, also results in abnormalities in the multicellular development of this organism, although there is no change in the rate of mitotic cell growth. This study has identified previously unsuspected molecular pathways which function in the cellular response to cisplatin and are required for normal morphogenesis, and underscores the complexity of the cellular response to cisplatin. These pathways provide potential targets for modulating the response to this important drug.

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Section: Discussionmentioning

confidence: 78%

Section: Mutant Cells Are Specifically Resistant To Cisplatinmentioning

confidence: 99%

Molecular basis for resistance to the anticancer drug cisplatin in Dictyostelium The GenBank accession numbers for the sequences reported in this paper are AF233610 (S-1-P lyase), AF233612 (PIP5K), AF233611 (P2Y purine receptor 1), AF233613 (CAAX prenyl protease) and AF233614 (unidentified gene).

Alexander

Schneider

et al. 2000

Microbiology

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“…The significance of the excision nuclease reaction is revealed by experiments across phyla. For instance, experiments on Dictyostelium discoideum, Saccharomyces cerevisiae and Escherichia coli have revealed that survival from exogenous mutagens depends on their capacity to increase expression of excision nuclease reagents above basal demands (Bronner et al 1992;Crowley and Hanawalt 1998;Yu et al 1998;Waters et al 1993). The mutagen cisplatin is a potent antineoplastic agent, however its effect is refractory to human tumors with elevated expression of the PIC-I reagent, XPA (Dabholkar et al 1994;Selvakumaran et al 2003).…”

Section: Discussionmentioning

confidence: 96%

Preincision complex-I from the excision nuclease reaction among cochlear spiral limbus and outer hair cells

Guthrie

2008

J Mol Hist

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The excision nuclease reaction defends the genome from endogenous and exogenous mutagens. The rate-limiting step in the reaction is facilitated by preincision complex-1 (PIC-1). PIC-1 is maintained by xeroderma pigmentosum A and C (XPA and XPC) through protein-protein interactions and DNA binding. XPA and XPC exhibit high-affinity for DNA adducts from the anticancer molecule, cisplatin. Systemic cisplatin treatment results in ubiquitous DNA adducts in the cochlea. Cochleae harvested from patients treated with cisplatin reveal dead outer hair cells among normal spiral limbus cells. Such discrepancy, suggest differences in genome defense repertoire among cochlear cells. The purpose of this study was to use cisplatin as a stimulus to examine XPA and XPC immunoreactivity among outer hair cells and spiral limbus cells. Fischer344 rats were treated with either one or two cycles of cisplatin, where each cycle lasted four days and separated by a 10 day rest period. Cochleae were harvested after each treatment cycle and four days after the second treatment cycle then processed for immunohistochemistry. Unlike spiral limbus cells, outer hair cells failed to acclimate to the cisplatin treatment cycles by regulating XPA and XPC immunoreactivity. These results imply that outer hair cells may have a limited capacity to mobilize PIC-I beyond basal demand.

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“…It also has been useful in the study of DNA repair [Deering, 1988;Bronner et al, 1992;Garcia et al, 2000]. An apurinic/apyrimidinic (AP) site-specific endonuclease (APEA) involved in DNA repair has been cloned and characterized from this organism [Freeland et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

Dictyostelium discoideum plasmid containing an AP‐endonuclease upstream sequence: Bleomycin induction of a luciferase reporter

Ling

Guyer

Deering

2001

Environ and Mol Mutagen

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A sequence of 1624 bp 5' to the apurinic/apyrimidinic (AP) endonuclease structural gene of Dictyostelium discoideum (APEA) has been inserted upstream of the luciferase reporter gene in pVTL2, an autonomously replicating nuclear plasmid in this organism. Cells transformed with this plasmid, designated pVTL-AL, displayed strong luciferase induction during treatment with the DNA-damaging agent bleomycin. For example, a luciferase activity of 45-fold above the constitutive level was observed for 20 hours of growth in axenic medium with 0.002 U/mL of bleomycin. The response was bleomycin concentration-dependent. Cell survival was greater than 90% for all treatments. The level of luciferase expression was highly dependent on the cell growth conditions, with the greatest induction observed for stationary phase axenically-grown cells. This effect may be related to a variation of plasmid copy number with growth conditions.

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Mutations affecting sensitivity of the cellular slime mold Dictyostelium discoideum to DNA-damaging agents

Cited by 20 publications

References 20 publications

Molecular basis for resistance to the anticancer drug cisplatin in Dictyostelium The GenBank accession numbers for the sequences reported in this paper are AF233610 (S-1-P lyase), AF233612 (PIP5K), AF233611 (P2Y purine receptor 1), AF233613 (CAAX prenyl protease) and AF233614 (unidentified gene).

Molecular basis for resistance to the anticancer drug cisplatin in Dictyostelium The GenBank accession numbers for the sequences reported in this paper are AF233610 (S-1-P lyase), AF233612 (PIP5K), AF233611 (P2Y purine receptor 1), AF233613 (CAAX prenyl protease) and AF233614 (unidentified gene).

Preincision complex-I from the excision nuclease reaction among cochlear spiral limbus and outer hair cells

Dictyostelium discoideum plasmid containing an AP‐endonuclease upstream sequence: Bleomycin induction of a luciferase reporter

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