Linking uracil base excision repair and 5-fluorouracil toxicity in yeast.

ABSTRACT: 5-fluorouracil (5-FU) is a widely used anticancer drug that disrupts pyrimidine nucleotide pool balances and leads to uracil incorporation in DNA, which is then recognized and removed by the uracil base excision repair (BER) pathway. Using complementary biochemical and genetic approaches we have examined the role of uracil BER in the cell killing mechanism of 5-FU. A yeast strain lacking the enzyme uracil DNA glycosylase (Ung1), which excises uracil from the DNA backbone leaving an abasic site, showed significant protection against the toxic effects of 5-FU, a G1/S cell cycle arrest phenotype, and accumulated massive amounts of U/A base pairs in its genome (approximately 4% of T/A pairs were now U/A). A strain lacking the major abasic site endonuclease of Saccharomyces cerevisiae (Apn1) sh

SUBMITTER: Seiple L 

PROVIDER: S-EPMC1326247 | biostudies-literature | 2006

REPOSITORIES: biostudies-literature