Three-dimensional nuclear organisation and the DNA replication timing program

In eukaryotic cells, genome duplication is temporally organised according to a program referred to as the replication-timing (RT) program. The RT of individual genomic domains strikingly parallels the three-dimensional architecture of their chromatin contacts and subnuclear distribution. However, it is unclear whether this correspondence is coincidental or whether it indicates a causal and regulatory relationship. In either case, the nature of the molecular mechanisms ensuring this spatio-temporal coordination is still unknown. Here, we review recent evidence that begins to uncover the existence of a shared molecular machinery at the core of the spatio-temporal co-regulation of DNA replication and genome architecture. Finally, we discuss the outstanding, key question of the biological role of their coordination.