Molecular Characterization and Elevated Cancer Risk Associated with DNA Repair Gene Variants

DNA is the repository of genetic information, and its integrity is crucial for genome stability. Several exogenous and endogenous factors damage the DNA and if not repaired lead to mutagenesis, genomic instability, and cancer. Several databases, including 1000 Genomes, Cbioportal, The Cancer Genome Atlas (TCGA), and the Catalog of Somatic Mutations in Cancer (COSMIC), continue to catalog several cancer-associated variants of DNA repair genes. However, the biological functions of these mutations and the effect in response to therapy are not known. We focus on studying: 1) how cancer-associated variants of DNA repair genes (such as MRE11 and POLQ) induce genomic instability; 2) cellular response of the cancer-associated variants to DNA damaging agents; and 3) how cancer-associated variants impact the efficacy of therapeutics. This particular research provides a commentary on the initial molecular cellular assays we employ to generate some of the cancer-associated variants of MRE11 and POLQ in vitro and their expression in mammalian cell lines