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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Mice
  • Point Mutation
  • Protein Binding
  • Protein Phosphatase 1 / chemistry
  • Protein Phosphatase 1 / metabolism
  • Telomere-Binding Proteins / chemistry*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism

Substances

  • Rif1 protein, mouse
  • Telomere-Binding Proteins
  • Protein Phosphatase 1