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  Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program

Foti, R., Gnan, S., Cornacchia, D., Dileep, V., Bulut-Karslioglu, A., Diehl, S., et al. (2016). Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program. Molecular Cell, 61, 260-273. doi:10.1016/j.molcel.2015.12.001.

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Foti, Rossana1, Author
Gnan, Stefano1, Author
Cornacchia, Daniela1, Author
Dileep, Vishnu1, Author
Bulut-Karslioglu, Aydan2, Author
Diehl, Sarah3, Author
Buness, Andreas1, Author
Klein, Felix A.1, Author
Huber, Wolfgang1, Author
Johnstone, Ewan1, Author
Loos, Remco1, Author
Bertone, Paul1, Author
Gilbert, David M.1, Author
Manke, Thomas3, Author
Jenuwein, Thomas2, Author           
Buonomo, Sara C.B.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              
3Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_persistent22              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2016-01-21
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2015.12.001
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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 61 Sequence Number: - Start / End Page: 260 - 273 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929