Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program.


DNA replication is temporally and spatially organized in all eukaryotes, yet the molecular control and biological function of the replication-timing program are unclear. Rif1 is required for normal genome-wide regulation of replication timing, but its molecular function is poorly understood. Here we show that in mouse embryonic stem cells, Rif1 coats late-replicating domains and, with Lamin B1, identifies most of the late-replicating genome. Rif1 is an essential determinant of replication timing of non-Lamin B1-bound late domains. We further demonstrate that Rif1 defines and restricts the interactions between replication-timing domains during the G1 phase, thereby revealing a function of Rif1 as organizer of nuclear architecture. Rif1 loss affects both number and replication-timing specificity of the interactions between replication-timing domains. In addition, during the S phase, Rif1 ensures that replication of interacting domains is temporally coordinated. In summary, our study identifies Rif1 as the molecular link between nuclear architecture and replication-timing establishment in mammals.

DOI: 10.1016/j.molcel.2015.12.001

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@article{Foti2016NuclearAO, title={Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program.}, author={Rossana Foti and Stefano Gnan and Daniela Cornacchia and Vishnu Dileep and Aydan Bulut-Karslioglu and Sarah Diehl and Andreas Buness and Felix A. Klein and Wolfgang Huber and Ewan R Johnstone and Remco Loos and Paul Bertone and David M. Gilbert and Thomas Manke and Thomas Jenuwein and Sara B C Buonomo}, journal={Molecular cell}, year={2016}, volume={61 2}, pages={260-73} }