| First Author | Foti R | Year | 2016 |
| Journal | Mol Cell | Volume | 61 |
| Issue | 2 | Pages | 260-73 |
| PubMed ID | 26725008 | Mgi Jnum | J:232860 |
| Mgi Id | MGI:5780354 | Doi | 10.1016/j.molcel.2015.12.001 |
| Citation | Foti R, et al. (2016) Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program. Mol Cell 61(2):260-73 |
| abstractText | 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. |
