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Nuclear organisation and replication timing are coupled through RIF1-PP1 interaction.

Gnan, Stefano ; Flyamer, Ilya M. ; Klein, Kyle N. ; Castelli, Eleonora ; Rapp, Alexander ; Maiser, Andreas ; Chen, Naiming ; Weber, Patrick ; Enervald, Elin ; Cardoso, M. Cristina ; Bickmore, Wendy A. ; Gilbert, David M. ; Buonomo, Sara C. B. (2021):
Nuclear organisation and replication timing are coupled through RIF1-PP1 interaction.
In: Nature communications, 12 (1), p. 2910. ISSN 2041-1723,
DOI: 10.1038/s41467-021-22899-2,
[Article]

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.

Item Type: Article
Erschienen: 2021
Creators: Gnan, Stefano ; Flyamer, Ilya M. ; Klein, Kyle N. ; Castelli, Eleonora ; Rapp, Alexander ; Maiser, Andreas ; Chen, Naiming ; Weber, Patrick ; Enervald, Elin ; Cardoso, M. Cristina ; Bickmore, Wendy A. ; Gilbert, David M. ; Buonomo, Sara C. B.
Title: Nuclear organisation and replication timing are coupled through RIF1-PP1 interaction.
Language: English
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.

Journal or Publication Title: Nature communications
Volume of the journal: 12
Issue Number: 1
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 25 May 2021 06:11
DOI: 10.1038/s41467-021-22899-2
Identification Number: pmid:34006872
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