Nicholas Adrian Willis

To explore how defects in stalled fork repair drives genomic instability and thereby cancer, I joined Dr. Ralph Scully’s group. I harnessed the replication fork barrier complex Tus/Ter from E. coli to stall incoming replication forks at a unique site in the mammalian chromosome. The Tus/Ter reporter allows for quantitation of error-free, error-prone, and mutagenic repair at stalled forks. The product of the breast and ovarian cancer predisposition gene, BRCA1 regulates stalled fork repair, supporting error-free and suppressing aberrant repair outcomes. Importantly, we find tandem duplications (TD), a important biomarker for BRCA1 loss in human cancers, are produced at stalled forks upon BRCA1 loss. Efforts focused towards characterizing the mechanism of TD formation is ongoing.