Principal Investigator Leona Samson
Project Website http://samsonlab.mit.edu/spontaneousmutagenesis.html
An increase in spontaneous mutations is associated with increased cancer risk. Our laboratory has shown that a simple imbalance between the first two enzymes involved in DNA base excision repair can increase the rate of spontaneous mutations several hundred-fold. Specifically, the S. cerevisiae MAG1 3-methyl-adenine DNA glycosylase, when expressed at high levels relative to the apurinic/apyrimidinic endonuclease (APN1), increases spontaneous mutation by up to approximately 600-fold in S. cerevisiae and approximately 200-fold in E. coli.
Genetic evidence suggests that, in yeast, the increased spontaneous mutation requires the generation of abasic sites and the processing of these sites by the REV1/REV3/REV7 lesion bypass pathway.