Knowledge Bank

Many cancers arise due to defects in the DNA repair process. Errors in the DNA repair process can cause a higher rate of mutations or lead to increased cell survival. BRCA1 is involved in DNA repair, and mutations in the BRCA1 gene are known to be associated with breast and ovarian cancer [22]. WWOX is the third most commonly depleted gene in cancers, and WWOX-deficient tumor cells are more resistant to chemotherapy and radiation therapy treatments [17, 18]. BRCA1 modulates homology directed repair (HDR) following a double-stranded break (DSB) in the DNA, and WWOX interacts with BRCA1 at serine 988. Previous research shows that in HeLa cells, WWOX expression inhibits HDR in the green fluorescent protein (GFP)-repair assay. We hypothesize that when WWOX is present, it interacts with BRCA1 to inhibit HDR from taking place when a sister chromatid is not available as a template. To test this, we established a Cas9 expressing cell line, initiated cuts at known genomic sequences, and analyzed the DNA sequence upon repair by innate cell mechanisms.