Overcoming natural replication barriers formed by DNA structures and the role of repositioning to the nuclear periphery

Abstract

Endogenous barriers to DNA replication, such as repetitive DNA, non-B DNA structures, and protein barriers present significant challenges to replication. Upon encountering one of these barriers, cells employ a number of strategies to ensure completion of replication. Some of these pathways operate at the stalled replication fork and others occur post-replicatively. These pathways vary both in their timing and the nuclear location in which they occur. Here we review how cells deal with endogenous sources of replication stress, with a focus on structure-forming DNA repeats, and our current understanding of how cells use nuclear positioning to facilitate the repair of natural replication barriers.