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Schematic overview of the pyrimidine biosynthetic pathway and its effect on the sensitivity of yeast cells to 5-FU under different conditions.

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posted on 2013-10-04, 02:48 authored by Mattias Carlsson, Marie Gustavsson, Guo-Zhen Hu, Eva Murén, Hans Ronne

(A) Wild type cells. 5-FU is taken up and converted to 5-FUMP, which competes with freshly synthesized UMP for incorporation into RNA. (B) In an arginine biosynthesis mutant, more carbamoyl-P is shunted into the pyrimidine biosynthesis, and the resulting increased in UMP reduces the amount of 5-FUMP that is incorporated into RNA. (C) In cells overexpressing CPA1, CPA2 or URA2, more carbamoyl-P is made, which also results in an increase in UMP that reduces the incorporation of 5-FUMP into RNA. (D) In cells overexpressing YAE1 or YJL055W, the amount of 5-FU that is incorporated into RNA is reduced by a mechanism that does not involve an increased pyrimidine biosynthesis.

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