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Updated: Mar 3, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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Published on: March 9, 2012

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MRE11 stability is regulated by CK2-dependent interaction with R2TP complex

P von Morgen1,2, K Burdova1, T G Flower3

  • 1Department of Cancer Cell Biology, Institute of Molecular Genetics of the ASCR, Prague, Czech Republic.

Oncogene
|April 25, 2017
PubMed

Insights

The MRN complex, vital for DNA repair, interacts with PIH1D1, a component of the R2TP complex. This interaction, regulated by CK2 phosphorylation, is crucial for MRN stability and DNA damage response.

Area of Science:

  • Molecular Biology
  • DNA Repair Mechanisms
  • Protein Complex Assembly

Background:

  • The MRN (MRE11-RAD50-NBS1) complex is critical for repairing DNA double-strand breaks and stalled replication forks.
  • Mutations in MRE11, an MRN subunit, cause ataxia-telangiectasia-like disorder (ATLD), a hereditary cancer-susceptibility disease.

Purpose of the Study:

  • To investigate the interaction between the MRN complex and the R2TP complex.
  • To elucidate the role of PIH1D1 and CK2 phosphorylation in regulating MRN complex stability and function.

Main Methods:

  • Co-immunoprecipitation assays to confirm MRE11-PIH1D1 interaction.
  • Site-directed mutagenesis to identify key phosphorylation sites.
  • Depletion studies using siRNA to assess the impact of PIH1D1 on MRE11 stability and DNA repair.
  • Analysis of MRE11 levels in ATLD patients and mouse models.

Main Results:

  • MRE11 directly interacts with PIH1D1, a subunit of the R2TP complex.
  • This interaction is mediated by CK2 phosphorylation of MRE11 at serines 558/561 and 688/689.
  • PIH1D1 depletion leads to MRE11 destabilization and impaired DNA damage repair.
  • Mutations abolishing PIH1D1 binding decrease MRE11 stability and MRN complex levels.

Conclusions:

  • The MRN complex is a novel substrate of the R2TP complex.
  • CK2-mediated phosphorylation regulates the interaction between MRN and R2TP, impacting MRN stability and DNA repair.
  • This finding provides new insights into the molecular mechanisms underlying ATLD and DNA damage response pathways.

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