The regulation of DNA replication is essential to ensure accurate duplication of the genome during the cell cycle. When this regulation is compromised, this results in replication stress and DNA damage. DNA replication stress is defined as the slowing or stalling of replication fork progression and/or DNA synthesis. This exposes single stranded DNA (ssDNA), and makes the fork susceptible to DNA damage. Oncogene-induced replication stress accounts for early DNA damage during tumorigenesis, and is an important driver of genomic instability in cancers. However, the mechanisms underlying this process are poorly understood. Oncogenes such as Ras and Cyclin E induce E2F-dependent transcription during the G1 phase of the cell cycle to drive premature entry into S phase causing replication stress. However, the lab has recently shown that prolonged E2F activity in S phase is also likely a crucial factor in the mechanisms of oncogene-induced replication stress, but this has not been characterized in any detail. My project aims to establish the consequences of deregulated G1/S transcription with respect to oncogene induced replication stress.