The replication checkpoint prevents fork stalling by reducing transcription

Authors

Heuze, J., Grassin, S., Pasero, P., Poli, J.

Abstract

The replication checkpoint is essential for maintaining genome stability during replication stress. The prevailing view is that, without this pathway, stalled DNA replication forks lose structural integrity and collapse, preventing replication resumption and ultimately causing cell death. Here, we show that transcription is a major cause of replication stress in budding yeast checkpoint mutants. Checkpoint signaling limits replication defects by reducing RNA polymerase II and III occupancy at highly transcribed genes, particularly those encoding ribosomal proteins. Reducing transcription at these loci reduces fork stalling and the sensitivity of checkpoint mutants to hydroxyurea-induced replication stress. In human cells, transcription inhibition likewise improves replication recovery when ATR is inhibited, suggesting that this function is conserved. Together, our findings extend the canonical view of critical checkpoint functions: in addition to stabilizing stalled forks, it actively reduces RNA polymerase roadblocks that would otherwise impede their progression.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 23 Oct 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.