The maintenance of genome integrity is critical for the suppression of cancer and premature ageing. Only recently has it become appreciated that DNA replication stress is a crucial driver of genomic instability. The timely progression of replisomes can be disrupted by lesions and secondary structures in the template, by bound proteins and by conflicts with the transcription machinery. A prolonged pause of the replisome then exposes single stranded DNA, which, due to its recombinogenic nature, can lead to genome rearrangements, fragile site expression and cell death. Importantly, some cancers present excessive endogenous levels of replication stress, which can be exploited for their clearance. In this conference, we aim to bring together scientists studying DNA replication and repair, with those interested in how DNA damage can influence cancer and ageing.
- Pathways for repair of damaged replication forks
- Systems for site-specific perturbation of replication
- Chromosome fragility caused by difficult-to-replicate loci – sources and roles of DNA repair proteins
- Replication perturbation as a driver of tumorigenesis and ageing
- Exploitation of replication defects in cancer treatment