| Oncogenesis is frequently accompanied by rampant genome instability, which fuels genetic heterogeneity and resistance to targeted cancer therapy. I have developed an approach that allows precise, quantitative measurement of genome instability in a high-throughput format in Saccharomyces cerevisiae. My approach takes advantage of the strongly DNA damage-inducible gene RNR3, in conjunction with the Reporter Synthetic Genetic Array methodology, to infer mutants exhibiting genome instability by assaying for increased Rnr3 abundance. We screen for genome instability across ~4200 non-essential mutant yeast alleles in untreated conditions and in the presence of the DNA damaging agent MMS. Our results provide broad insights into the cellular processes and pathways required for genome maintenance. Preliminary follow-up work suggests that several genes have bona fide roles in the maintenance of genome stability. In addition, I conducted both screens in their entirety on two, highly orthogonal fluorescence imaging platforms and compared their reproducibility and sensitivity. |
