The pol3-t hyperrecombination phenotype and DNA damage-induced recombination in Saccharomyces cerevisiae is RAD50 dependent.

The DNA polymerase delta (POL3/CDC2) allele pol3-t of Saccharomyces cerevisiae has previously been shown to be sensitive to methylmethanesulfonate (MMS) and has been proposed to be involved in base excision repair. Our results, however, show that the pol3-t mutation is synergistic for MMS sensitivity with MAG1, a known base excision ...
repair gene, but it is epistatic with rad50Delta, suggesting that POL3 may be involved not only in base excision repair but also in a RAD50 dependent function. We further studied the interaction of pol3-t with rad50Delta by examining their effect on spontaneous, MMS-, UV-, and ionizing radiation-induced intrachromosomal recombination. We found that rad50Delta completely abolishes the elevated spontaneous frequency of intrachromosomal recombination in the pol3-t mutant and significantly decreases UV- and MMS-induced recombination in both POL3 and pol3-t strains. Interestingly, rad50Delta had no effect on gamma-ray-induced recombination in both backgrounds between 0 and 50 Gy. Finally, the deletion of RAD50 had no effect on the elevated frequency of homologous integration conferred by the pol3-t mutation. RAD50 is possibly involved in resolution of replication forks that are stalled by mutagen-induced external DNA damage, or internal DNA damage produced by growing the pol3-t mutant at the restrictive temperature.
Mesh Terms:
Alleles, Cell Survival, DNA Damage, DNA Polymerase III, DNA Repair, DNA-Binding Proteins, Dose-Response Relationship, Drug, Epistasis, Genetic, Gamma Rays, Methyl Methanesulfonate, Mutagens, Mutation, Phenotype, Radiation Dosage, Recombination, Genetic, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ultraviolet Rays
J. Biomed. Biotechnol.
Date: Oct. 17, 2009
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