Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage.

ABSTRACT: Recent work established DNA replication stress as a crucial driver of genomic instability and a key event at the onset of cancer. Post-translational modifications play an important role in the cellular response to replication stress by regulating the activity of key components to prevent replication-stress-induced DNA damage. Here, we establish a far greater role for transcriptional control in determining the outcome of replication-stress-induced events than previously suspected. Sustained E2F-dependent transcription is both required and sufficient for many crucial checkpoint functions, including fork stalling, stabilization, and resolution. Importantly, we also find that, in the context of oncogene-induced replication stress, where increased E2F activity is thought to cause replication st

SUBMITTER: Bertoli C 

PROVIDER: S-EPMC4893157 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature