In a new study published today in Nature Communications, researchers reveal how replication stress (which can lead to later genetic mutations) can be caused by an increase in activity of a cell’s own transcription machinery.
The research shows that in cells containing an activated version of the cancer-promoting gene (or ‘oncogene’) H-RasV12, the rate of transcription and protein production is dramatically increased. The resulting RNA can form unusual structures called ‘R-loops’ within the DNA of the cell, which in turn cause DNA damage and replication stress.
Although it was previously suspected that H-RasV12 caused increases in transcription, this study provides the first solid evidence of the mechanism, as well as the first description of the role of this oncogene in R-loop formation.