Figure 3.

Main sources of replication stress. DNA replication progression is constantly challenged. Replication stress, a major source of genome instability, is defined as the temporary slowing or stalling of RFs due to the encountered obstacles or DNA lesions induced by both endogenous and exogenous agents. Among them are topological obstacles such as G-quadruplexes, the shortage of replication resources, oncogene activation, DNA protein crosslinks, and DNA-RNA hybrids (orange strand). Additionally, several chemicals can induce replication stress by the inhibition of key enzymes for replication or generation of blocking lesions (light blue).