Restoring genome stability and tumor suppression in BRCA1 deficient cells

PROJECT NARRATIVE: Inherited BRCA1 mutations predispose women to the more lethal forms of both breast (basal-like triple- negative) and ovarian (high-grade serous) cancer. Two aspects of BRCA1 function are proposed to be especially important for genome stability and, in turn, tumor suppression: DNA break repair by homologous recombination (DSBR-HR) and stalled replication fork (SRF) stability. This study will examine whether molecular interventions that restore SRF stability (e.g., by inhibition of the SMARCAL1 translocase) will suppress the tumorigenicity of BRCA1-mutant cells.