1. Mouse Rif1 is a regulatory subunit of protein phosphatase 1 (PP1)
- Author
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Darren J. Hart, Tania Auchynnikava, Rasa Sukackaite, Maja Köhn, Elin Enervald, Martin Blackledge, Guangyou Duan, Philippe J. Mas, Sara B.C. Buonomo, Daniela Cornacchia, Malene Ringkjøbing Jensen, European Molecular Biology Laboratory [Grenoble] (EMBL), European Molecular Biology Laboratory, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), European Molecular Biology Laboratory [Heidelberg] (EMBL), Wellcome Trust Center for Cell Biology, University of Edinburgh, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,DNA repair ,Science ,Protein subunit ,Telomere-Binding Proteins ,Mutagenesis (molecular biology technique) ,Biology ,Article ,Cell Line ,Mice ,03 medical and health sciences ,Rif1 ,Protein Phosphatase 1 ,DNA Replication Timing ,Animals ,Point Mutation ,protein phosphatase 1 (PP1) ,General ,Genetics ,Binding Sites ,Multidisciplinary ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Signal transducing adaptor protein ,Cell biology ,Chromatin ,030104 developmental biology ,Medicine ,Nuclear lamina ,Function (biology) ,Protein Binding ,adaptor protein - 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.
- Published
- 2017
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