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. und Buonomo, Sara C. B. (2021): Nuclear organisation and replication timing are coupled through RIF1-PP1 interaction. In: Nature Communications, Bd. 12, Nr. 1, 2910

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. How nuclear architecture overall affects the replication-timing programme is not yet clear. Here the authors reveal RIF1's dual role as a chromatin-interaction scaffold and regulator of replication timing that allows the coordination of these two aspects of nuclear function.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Biologie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie
• ISSN: 2041-1723
• Sprache: Englisch