ATR inhibition affects RNA Polymerase II transcription during S-phase

Transcription and replication are the key processes in cell growth and division that utilize DNA as their template. Concurrently, conflicts between the two processes increase genome instability levels. Evidence in the literature indicate that transcription and replication can however coexist, suggesting the requirement for cellular mechanisms to avoid reciprocal interference. To identify factors important in this regulatory process, we performed a screening of known DNA damage response proteins. Among the factors assessed, we found that specifically inhibition of ATR affected cells’ ability to replicate long transcribed genes, impacting also on cells’ ability to transcribe these genes. However, ATR activity was also required later during S-phase the control transcription activity on all genes. Dissecting which of ATR’s roles is important for this process, we uncovered that SMARCAL1 is likewise required to regulate genes transcription later during S-phase. Altogether, we have uncovered how DNA damage response factors are required to support the replication of transcribed regions, but also how their role extends to regulate also genes transcription levels during S-phase.