Nuclear organisation and replication timing are coupled through RIF1–PP1 interaction

Stefano Gnan, Ilya M. Flyamer, Kyle N. Klein, Eleonora Castelli, Alexander Rapp, Andreas Maiser, Naiming Chen, Patrick Weber, Elin Enervald, M. Cristina Cardoso, Wendy A. Bickmore, David M. Gilbert and Sara C. B. Buonomo ()
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Stefano Gnan: European Molecular Biology Laboratory (EMBL Rome)
Ilya M. Flyamer: University of Edinburgh
Kyle N. Klein: Florida State University
Eleonora Castelli: School of Biological Sciences University of Edinburgh
Alexander Rapp: Technical University of Darmstadt
Andreas Maiser: LMU Munich
Naiming Chen: School of Biological Sciences University of Edinburgh
Patrick Weber: Technical University of Darmstadt
Elin Enervald: European Molecular Biology Laboratory (EMBL Rome)
M. Cristina Cardoso: Technical University of Darmstadt
Wendy A. Bickmore: University of Edinburgh
David M. Gilbert: Florida State University
Sara C. B. Buonomo: European Molecular Biology Laboratory (EMBL Rome)

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Three-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing programme and, if so, how. Here we demonstrate that RIF1 is a molecular hub that co-regulates both processes. Both nuclear organisation and replication timing depend upon the interaction between RIF1 and PP1. However, whereas nuclear architecture requires the full complement of RIF1 and its interaction with PP1, replication timing is not sensitive to RIF1 dosage. The role of RIF1 in replication timing also extends beyond its interaction with PP1. Availing of this separation-of-function approach, we have therefore identified in RIF1 dual function the molecular bases of the co-dependency of the replication-timing programme and nuclear architecture.

Date: 2021
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DOI: 10.1038/s41467-021-22899-2

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