Fig. 7. TC expression in endothelial cells results in senescence and genomic instability.

Schematic showing how TC expression in endothelial cells results in hypertranscription, leading to the accumulation of DNA damage which in turn causes S phase arrest. As TC-expressing endothelial cells have impaired HR, as shown by reduced BRCA1 and RAD51 foci formation, many become senescent as the large amount of DNA damage is not repaired. These cells have increased p16 expression and remain arrested. In a subset of cells an error-prone DNA repair pathway will take over, leaving these vulnerable to acquiring growth-promoting secondary mutation.