A new study by Liakos et al. (Fousteri lab) published in Nucleic Acids Research, links transcription pre-initiation assembly dynamics in response to genotoxic stress with cancer mutational landscapes.
By employing high throughput approaches in combination with time- and inhibitor-resolved measurements the authors monitored the depletion and re-assembly kinetics of pre-initiating RNA Polymerase II complexes as they occur in vivo in steady-state and after exposure to UV irradiation.
They found that the majority of active genes show a faster frequency of pre-initiation complex (PIC) assembly formation compared to the non-irradiated cells early after damage induction. Moreover, they identified groups of genes with significantly different PIC assembly dynamics after UV that present distinct rates of UV-related mutational signatures in melanoma tumours, providing functional relevance to the importance of keeping transcription initiation active during UV recovery.
Anastasios Liakos*, Anna-Chloe Synacheri, Dimitris Konstantopoulos, Georgios C Stefos, Matthieu D Lavigne, Maria Fousteri* (2023). Enhanced frequency of transcription pre-initiation complexes assembly after exposure to UV irradiation results in increased repair activity and reduced probabilities for mutagenesis, Nucleic Acids Research, gkad593, https://doi.org/10.1093/nar/gkad593