Transcription and replication stress in cancer

Cancer is a disease of genomic instability, and one source of genomic instability is replication stress. Replication stress occurs when DNA replication fork progression is inhibited, which causes mutagenic DNA damage and defects in mitotic chromosome segregation. There is plenty of evidence for replication stress in cancer cells, but little is known about its underlying causes.
Our recent data suggest that a common aberration of cancer cells, namely increased transcription, can cause spontaneous replication stress. Transcription can obstruct replication because it uses the same template, and by generating RNA-DNA hybrids called R-loops that stall replication and cause DNA damage. This project will further investigate the role of transcription and R-loops as a cause of in replication stress, and its implications for cancer treatment.

This self-funded PhD project combines our expertise in labelling of nascent DNA with nucleoside analogues (DNA fibre method) to study mammalian replication fork progression with standard cell and molecular biology techniques to investigate transcription, R-loops and replication stress in cancer cells.