Grant: Project Grant

Mutations in DNA are a driving force in cancer initiation, progression and therapy resistance. Some mutations arise from normal functions involving DNA. These functions include copying DNA during cell division, and transcribing DNA into RNA messages that control the production of proteins in the cell. These two independent processes, termed DNA replication and transcription, must occur at the same time on the same DNA, and therefore they can interfere with one another. We now know that these replication-transcription conflicts are a potential source of DNA damage and mutations and are thought to be influenced by breast cancer susceptibility genes. This proposal will clearly define new roles for breast cancer tumour suppressor genes in preventing replication-transcription conflicts, and survey the prevalence of such conflicts in normal cells from individuals with elevated 5-year risk for breast cancer and in early and late stage breast cancer samples. Our hope is to find new ways to selectively eliminate breast cancer cells experiencing high levels of replication-transcription collisions.