Maintaining genome stability at the replication fork

Abstract

Problems in DNA replication can induce chromosome rearrangements that are often associated with pathological disorders. Natural elements such as unusual DNA structures, fragile zones and DNA-binding proteins impede replication and can impact on replication fork stability and progression. Replication induces changes in DNA topology, which affect replication and replication-associated repair processes. Replication checkpoints have key roles in promoting replication fork stability. Different types of DNA lesions elicit the action of diverse damage-tolerance pathways that restore replication fork progression or promote DNA repair. Together with the checkpoint-mediated pathway, small ubiquitin-related modifier (SUMO) and ubiquitin modifications are crucial in regulating the stability and activity of key components of DNA replication and repair machineries.