A pre-requisite for successful cell division in any organism is synthesis of an accurate copy of the genetic information needed for survival. This copying process is a mammoth task, given the amount of DNA that must be duplicated, but potential blocks to replication fork movement also pose a challenge for genome duplication. Damage to the template inhibits the replication machinery but proteins bound to the template such as RNA polymerases also present barriers to replication. This review discusses recent results from Escherichia coli that shed light on the roles of helicases in overcoming protein–DNA barriers to replication and that may illustrate fundamental aspects of how duplication of protein-bound DNA is underpinned in all organisms.

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