ASaccharomyces cerevisiaephleomycin-sensitive mutant, phl40, is defective in theRAD6DNA repair gene
- 1 December 1996
- journal article
- research article
- Published by Canadian Science Publishing in Canadian Journal of Microbiology
- Vol. 42 (12), 1263-1266
- https://doi.org/10.1139/m96-164
Abstract
The antibiotic bleomycin is used as an anticancer agent for treating a variety of tumours. The antitumour effect of bleomycin is related to its ability to produce lesions such as apurinic/apyrimidinic sites and single- and double-strand breaks in the cellular DNA. Phleomycin is a structurally related form of bleomycin, but it is not used as an anticancer agent. While phleomycin can also damage DNA, neither the exact nature of these DNA lesions nor the cellular process that repairs phleomycin-induced DNA lesions is known. As a first step to understand how eukaryotic cells provide resistance to phleomycin, we used the yeast Saccharomyces cerevisiae as a model system. Several phleomycin-sensitive mutants were generated following γ-radiation treatment and among these mutants, phl40 was found to be the most sensitive to phleomycin. Molecular analysis revealed that the mutant phl40 harbored a mutation in the DNA repair gene RAD6. Moreover, a functional copy of the RAD6 gene restored full phleomycin resistance to strain phl40. Our findings indicate that the RAD6 protein is essential for yeast cellular resistance to phleomycin.Key words: yeast, phleomycin, DNA repair, RAD6.Keywords
This publication has 21 references indexed in Scilit:
- Sequence Specific Double-Strand Cleavage of DNA by Fe-Bleomycin. 1. The Detection of Sequence-Specific Double-Strand Breaks Using Hairpin OligonucleotidesBiochemistry, 1995
- Genetic changes and bioassays in bleomycin- and phleomycin-treated cells, and their relationship to chromosomal breaksMutation Research/DNA Repair, 1995
- DNA REPAIR GENES AND PROTEINS OF SACCHAROMYCES CEREVISIAEAnnual Review of Genetics, 1993
- Isotope effects on the cleavage of DNA by bleomycin: Mechanism and modulationBiochemistry, 1993
- Spontaneous cleavage of bleomycin-induced abasic sites in chromatin and their mutagenicity in mammalian shuttle vectorsBiochemistry, 1993
- The extremely conserved amino terminus of RAD6 ubiquitin-conjugating enzyme is essential for amino-end rule-dependent protein degradation.Genes & Development, 1993
- THE UBIQUITIN SYSTEM FOR PROTEIN DEGRADATIONAnnual Review of Biochemistry, 1992
- Identification and quantitation of the lesion accompanying base release in bleomycin-mediated DNA degradationJournal of the American Chemical Society, 1990
- The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzymeNature, 1987
- Copper(II).bleomycin, iron(III).bleomycin, and copper(II).phleomycin: comparative study of deoxyribonucleic acid bindingBiochemistry, 1981