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Sci Rep. 2017 May 18;7(1):2119. doi: 10.1038/s41598-017-01910-1.

Mouse Rif1 is a regulatory subunit of protein phosphatase 1 (PP1).

Author information

1
European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, 6 rue Jules Horowitz, 38042, France.
2
European Molecular Biology Laboratory, Monterotondo Outstation, Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00015, Monterotondo, Italy.
3
Thermo Fisher Scientific Baltics, UAB, Graiciuno 8, 02241, Vilnius, Lithuania.
4
Memorial Sloan Kettering Cancer Center, Center for Stem Cell Biology, Lorenz Studer Group, Rockefeller Research Laboratories, 430 E 67th Street, 10065, New York, NY, USA.
5
Institut de Biologie Structurale (IBS), CEA, CNRS, Université Grenoble Alpes, 38044, Grenoble, France.
6
Institute of Cell Biology, School of Biological Sciences University of Edinburgh, Roger Land, Building, Alexander Crum Brown Road, Edinburgh, EH9 3FF, UK.
7
Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117, Heidelberg, Germany.
8
School of Life Sciences, Qilu Normal University, Wenbo Road 2, 250200, Jinan, China.
9
Wellcome Trust Center for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh, EH9 3BF, UK.
10
Faculty of Biology and Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Schänzlestr 18, 79104, Freiburg, Germany.
11
European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, 6 rue Jules Horowitz, 38042, France. darren.hart@ibs.fr.
12
Institut de Biologie Structurale (IBS), CEA, CNRS, Université Grenoble Alpes, 38044, Grenoble, France. darren.hart@ibs.fr.
13
European Molecular Biology Laboratory, Monterotondo Outstation, Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00015, Monterotondo, Italy. sara.buonomo@ed.ac.uk.
14
Institute of Cell Biology, School of Biological Sciences University of Edinburgh, Roger Land, Building, Alexander Crum Brown Road, Edinburgh, EH9 3FF, UK. sara.buonomo@ed.ac.uk.

Abstract

Rif1 is a conserved protein that plays essential roles in orchestrating DNA replication timing, controlling nuclear architecture, telomere length and DNA repair. However, the relationship between these different roles, as well as the molecular basis of Rif1 function is still unclear. The association of Rif1 with insoluble nuclear lamina has thus far hampered exhaustive characterization of the associated protein complexes. We devised a protocol that overcomes this problem, and were thus able to discover a number of novel Rif1 interactors, involved in chromatin metabolism and phosphorylation. Among them, we focus here on PP1. Data from different systems have suggested that Rif1-PP1 interaction is conserved and has important biological roles. Using mutagenesis, NMR, isothermal calorimetry and surface plasmon resonance we demonstrate that Rif1 is a high-affinity PP1 adaptor, able to out-compete the well-established PP1-inhibitor I2 in vitro. Our conclusions have important implications for understanding Rif1 diverse roles and the relationship between the biological processes controlled by Rif1.

PMID:
28522851
PMCID:
PMC5437018
DOI:
10.1038/s41598-017-01910-1
[Indexed for MEDLINE]
Free PMC Article

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