Control of 5‐FOA and 5‐FU resistance by <i>Saccharomyces cerevisiae YJL055W</i>

Ko, Nolan; Nishihama, Ryuichi; Pringle, John R.

doi:10.1002/yea.1554

Cited by 17 publications

(9 citation statements)

References 16 publications

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“…Several possible target genes for Hms1p have been identified by phenotypic activation [18]. The YJL055W gene is known to confer resistance to 5-FOA when overexpressed, and further testing showed that it also confers resistance to 5-FU [19]. Conversely, a yjl055w mutant is sensitive to purine analogs [20].…”

Section: Resultsmentioning

confidence: 99%

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A Ham1p-Dependent Mechanism and Modulation of the Pyrimidine Biosynthetic Pathway Can Both Confer Resistance to 5-Fluorouracil in Yeast

Carlsson

Gustavsson

et al. 2013

PLoS ONE

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5-Fluorouracil (5-FU) is an anticancer drug and pyrimidine analogue. A problem in 5-FU therapy is acquired resistance to the drug. To find out more about the mechanisms of resistance, we screened a plasmid library in yeast for genes that confer 5-FU resistance when overexpressed. We cloned five genes: CPA1, CPA2, HMS1, HAM1 and YJL055W. CPA1 and CPA2 encode a carbamoyl phosphate synthase involved in arginine biosynthesis and HMS1 a helix-loop-helix transcription factor. Our results suggest that CPA1, CPA2, and HMS1 confer 5-FU resistance by stimulating pyrimidine biosynthesis. Thus, they are unable to confer 5-FU resistance in a ura2 mutant, and inhibit the uptake and incorporation into RNA of both uracil and 5-FU. In contrast, HAM1 and YJL055W confer 5-FU resistance in a ura2 mutant, and selectively inhibit incorporation into RNA of 5-FU but not uracil. HAM1 is the strongest resistance gene, but it partially depends on YJL055W for its function. This suggests that HAM1 and YJL055W function together in mediating resistance to 5-FU. Ham1p encodes an inosine triphosphate pyrophosphatase that has been implicated in resistance to purine analogues. Our results suggest that Ham1p could have a broader specificity that includes 5-FUTP and other pyrimidine analogoue triphosphates.

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Section: Resultsmentioning

confidence: 99%

“…Conversely, a yjl055w mutant is sensitive to purine analogs [20]. It has therefore been proposed that YJL055W may function in detoxification of base analogs [19].…”

Section: Resultsmentioning

confidence: 99%

A Ham1p-Dependent Mechanism and Modulation of the Pyrimidine Biosynthetic Pathway Can Both Confer Resistance to 5-Fluorouracil in Yeast

Carlsson

Gustavsson

et al. 2013

PLoS ONE

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“…From 35 transformants identified initially, plasmid recovery and retransformation yielded 22 plasmids that reproducibly rescued strain MOY66. Subcloning and/or deletion analyses identified the suppressor genes in 16 of these plasmids as (numbers of isolates in parentheses) CYK3 (3), HOF1 (2), RHO1 (2), KDX1 (2), RGD2 (1), cdc24* (1), PAP1 (2), NAB6 (2), and the 5-FOA resistance gene YJL055W (1; Ko et al, 2008). The remaining six plasmids contained distinct genome fragments in which the suppressor genes have not been determined.…”

Section: Identification Of Multicopy Suppressors For Cyk3 Hof1mentioning

confidence: 99%

Distinct roles of Rho1, Cdc42, and Cyk3 in septum formation and abscission during yeast cytokinesis

Onishi

Nishihama

et al. 2013

Journal of Cell Biology

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109

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“…We selected URA3 as the conditional killer gene; it codes for the protein orotidine-5′-phosphate (OMP) decarboxylase which converts 5-FOA into the cytotoxic pyramidine analog 5-fluorouracil (5-FU) (21). 5-FU misincorporates into RNA and DNA in place of uracil or thymine, hampering normal RNA and DNA processing, and leads to cell arrest (22). In strains lacking the URA3 gene, 5-FOA is not converted into 5-FU, and cell growth is not affected (23).…”

Section: Resultsmentioning

confidence: 99%

A synthetic circuit for selectively arresting daughter cells to create aging populations

Afonso

Silver

Ajo‐Franklin

2010

Nucleic Acids Research

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The ability to engineer genetic programs governing cell fate will permit new safeguards for engineered organisms and will further the biological understanding of differentiation and aging. Here, we have designed, built and implemented a genetic device in the budding yeast Saccharomyces cerevisiae that controls cell-cycle progression selectively in daughter cells. The synthetic device was built in a modular fashion by combining timing elements that are coupled to the cell cycle, i.e. cell-cycle specific promoters and protein degradation domains, and an enzymatic domain which conditionally confers cell arrest. Thus, in the presence of a drug, the device is designed to arrest growth of only newly-divided daughter cells in the population. Indeed, while the engineered cells grow normally in the absence of drug, with the drug the engineered cells display reduced, linear growth on the population level. Fluorescence microscopy of single cells shows that the device induces cell arrest exclusively in daughter cells and radically shifts the age distribution of the resulting population towards older cells. This device, termed the ‘daughter arrester’, provides a blueprint for more advanced devices that mimic developmental processes by having control over cell growth and death.

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Control of 5‐FOA and 5‐FU resistance by Saccharomyces cerevisiae YJL055W

Cited by 17 publications

References 16 publications

A Ham1p-Dependent Mechanism and Modulation of the Pyrimidine Biosynthetic Pathway Can Both Confer Resistance to 5-Fluorouracil in Yeast

A Ham1p-Dependent Mechanism and Modulation of the Pyrimidine Biosynthetic Pathway Can Both Confer Resistance to 5-Fluorouracil in Yeast

Distinct roles of Rho1, Cdc42, and Cyk3 in septum formation and abscission during yeast cytokinesis

A synthetic circuit for selectively arresting daughter cells to create aging populations

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