ATR activity regulates DNA replication and RNA polymerase II transcription during S-phase

Transcription and replication both utilize DNA as a template. However, even though conflicts between transcription and replication can induce genome instability, recent data have shown that both coexist temporally and spatially. We have now identified that cells employ multiple mechanisms to control transcription activity in S-phase. Our data show that transcription can be regulated by reducing RNA polymerase II loading on genes or by accumulating it on the promoter and preventing its progress into the gene body; moreover, this can occur on all transcribed genes or only on those replicated at that moment, and all these regulations appear controlled by ATR activity. Finally, we found a correlation between the genes most affected in our system and those with altered expression in patients with cancer with deregulated ATR, potentially linking ATR's roles in regulating transcription activity during S-phase to phenotypes found in patients with cancer.