Cell cycle regulated transcription and control of genome integrity

Cancer is a group of diseases in which cells continue to multiply in an unregulated manner. The main regulation of initiation of a new cell division cycle is imposed during a specific phase of the cell cycle called G1. Proteins that control exit from G1-phase, including those involved in regulating G1-S transcription, are often found mutated in human tumour cells, suggesting that inactivation of this pathway may be necessary for tumour development. DNA structure checkpoints restrict cell-cycle progression in response to the detection of abnormalities in the genetic material. When these checkpoints fail, cells are at risk of increased genetic abnormalities, phenomena that are associated with tumour development. My previous work showed that the G1-S transcriptional regulatory network is a target of DNA structure checkpoints. The goal of my future research programme is to build on this work to understand the interplay between the DNA structure checkpoints and the regulation of G1-S transcription. To do this, I will employ a combination of biochemical and molecular biological techniques. I believe that understanding the mechanisms governing regulation of G1-S transcription in response to genotoxic stress and during the cell-cycle will provide new insights into the genesis and treatment of human cancer.