The symptoms of Hereditary Nonpolyposis Colerectal Cancer (HNPCC) are caused by inherited defects in the DNA Mismatch Repair Mechanism (MMR), a mechanism responsible for fixing the mutations that occur during DNA replication. Components of MMR, MSH2 and MSH6 form complexes to recognize the mutations and then recruit exonucleases for excision. Because MMR keeps the overall mutation rate in check, defects in MMR, such as mutations in MSH2, are often linked to HNPCC. The goal of this project is to determine whether a single nucleotide polymorphism (SNP) in MSH2 genes results in higher mutation rate. A series of experiments was conducted to determine that the type of SNP present in MSH2 gene is an M718I mutation. Finally, yeast strains carrying mutated MSH2 and wild-type MSH2 were analyzed by FOA assay. Our data indicated that yeast transformed with wild-type MSH2 had the lowest mutation rate, while the highest mutation rate came from yeasts transformed with the mutated MSH2. Our data could help determine whether a person is more susceptible to HNPCC based on the type of SNP present in MSH2. A thorough functional characterization of the existing SNPs in MSH2 could enhance risk assessment for HNPCC.
