DNA replication stress

[5] In addition to stalling and maintaining the fork structure, protein phosphorylation can also create a signal cascade for replication restart.

In vertebrate cells, replication of an ICL-containing chromatin template triggers recruitment of more than 90 DNA repair and genome maintenance factors.

Mechanisms that process damaged DNA in coordination with the replisome in order to maintain replication fork progression are considered to be examples of replication-coupled repair.

[9] Replication fork collapse at leading strand nicks generates resected single-ended double-strand breaks that can be repaired by homologous recombination.

[10] These stresses include, but are not limited to, DNA damage, excessive compacting of chromatin (preventing replisome access), over-expression of oncogenes,[11] or difficult-to-replicate genome structures.

[14] The events that lead to genome instability occur in the cell cycle prior to mitosis, specifically in the S phase.

[17] Normal replication stress occurs at low to mild levels and induces genomic instability, which can lead to tumorigenesis and cancer progression.

In one study, researchers sought to determine the effects of inducing high levels of replication stress on cancer cells.

Results from this study show that weakening oncogenic signaling or intensifying DNA replication stress can alter carcinogenic potential, and can be manipulated therapeutically.