Nuclear organisation and replication timing are connected through Nuclear organisation and replication timing are connected through RIF1

The parallel regulation of nuclear three-dimensional organisation and the temporal order of replication of different genomic regions has suggested the hypothesis of their interdependence. However, it remains unknown weather nuclear architecture overall plays an instructive role in the replication-timing program. Here we demonstrate that they are indeed coupled and that RIF1 is the molecular hub that connects/coordinates them. Both nuclear organisation and replication timing depend upon RIF1-PP1 interaction. However, while nuclear architecture requires the full complement of RIF1 and its interaction with PP1, replication timing is not sensitive to RIF1 dosage and RIF1's role in this process extends beyond the interaction with PP1.