Replication Fork Barriers and Topological Barriers: Progression of DNA Replication Relies on DNA Topology Ahead of Forks

Abstract

During replication, the topology of DNA changes continuously in response to well-known activities of DNA helicases, polymerases, and topoisomerases. However, replisomes do not always progress at a constant speed and can slow-down and even stall at precise sites. The way these changes in the rate of replisome progression affect DNA topology is not yet well understood. The interplay of DNA topology and replication in several cases where progression of replication forks reacts differently to changes in DNA topology ahead is discussed here. It is proposed, there are at least two types of replication fork barriers: those that behave also as topological barriers and those that do not. Two-Dimensional (2D) agarose gel electrophoresis is the method of choice to distinguish between these two different types of replication fork barriers.

Linking replication stress with replication dynamics in Vicia faba root meristem cells

“…A) is characterized by a large number of small replication foci, primarily related to transcriptionally active euchromatin (EC) regions. EC is preferably replicated at early-S stage, because transcription-replication collision is one of the most dangerous internal factors that may cause fork stalling and genome instability [2,26,61,62]. The mid-S phase is usually a short transition, where early-replicating factories finish their job (so the sand-like type of labeling slowly fades) and late-replicating factories are activated (Figure 3.…”

“…The progression of replication forks during DNA replication is frequently hindered by various factors, both exogenous and internal. DNA damage, regions of active transcription or dense chromatin may cause fork stalling or even stop them and result in the phenomena generally described as replication stress [1][2][3][4]. Stalled replication forks pose a threat to the integrity of the genome and are very potent inducers of genome alterations associated with cancer progression.…”