Cellular regulation and stability of DNA replication forks in eukaryotic cells

Abstract

Genomic DNA in yeast and human cells harbors approximately 2000 and a few million DNA replication barriers, respectively. These barriers result in frequent replication fork stalling, causing tremendous stress on DNA replication. Stalled replication forks are unstable and tend to collapse as a result of the intrinsic instability of replisomes. Checkpoint and chromsfork (chromatin compaction stabilizes stalling replication forks) controls have been shown to be essential for stabilizing stalled replication forks. However, their underlying regulatory mechanisms are only partially understood. To give some perspectives, we must know the current situation in the field. Thus, this review succinctly goes through our current understanding of replication barriers, replisomes, replication forks, types of fork collapse, checkpoint, and chromsfork control. We also give our views on some controversial issues in this field, and hopefully, they will be helpful for future studies. In the final section on perspectives, some key questions are outlined. Due to space limitations, many excellent works are not discussed here, and readers are referred to other excellent review articles.