Transcription And The Maintenance Of Genome Stability

Over the last decade it has become increasingly evident that transcription is closely integrated with other DNA-related processes, such as chromatin dynamics, DNA replication and repair. Indeed, the essential process of expressing genes comes at a cost: the movement of RNA polymerases through chromatin is associated with significant genome instability. RNA Polymerase II stalling, arrest, and/or backtracking - collectively referred to as transcription stress - thus generates a cellular response akin to the DNA damage response, and constantly needs to be contended with to avoid DNA damage. The factors and mechanisms involved in suppressing transcription-associated genome instability remain poorly understood. Conversely, DNA damage itself, such as that induced by UV-irradiation, also greatly affects transcription. Indeed, UV-damage triggers rapid reduction in global RNA synthesis and changes to mRNA splicing, but the molecular details and underlying mechanisms again remain unclear. In this talk, our recent advances in understanding the interface between transcription and the maintenance of genome integrity will be outlined.