Related Experiment Video

Updated: Jul 16, 2025

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins
12:47

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins

Published on: December 27, 2016

18.8K

The molecular details of a novel phosphorylation-dependent interaction between MRN and the SOSS complex

Serene El-Kamand1, Mark N Adams2, Jacqueline M Matthews3

  • 1School of Science, Western Sydney University, Penrith, New South Wales, Australia.

Protein Science : a Publication of the Protein Society
|September 14, 2023
PubMed

Insights

The study reveals how INTS3 protein binds to Nbs1, a key component of the MRN complex, through phosphorylation. This interaction is crucial for recruiting the MRN complex to DNA double-strand breaks (DSBs) for repair.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Homologous recombination repairs DNA double-strand breaks (DSBs), maintaining genome integrity.
  • The Mre11-Rad50-Nbs1 (MRN) complex and hSSB1 (sensor of single-stranded DNA) are vital for DSB repair.
  • Previous work showed hSSB1 binds Nbs1, and Integrator Complex Subunit 3 (INTS3) also interacts with Nbs1.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying the interaction between INTS3 and Nbs1.
  • To understand how INTS3 contributes to the recruitment of the MRN complex to DSBs.

Main Methods:

  • In silico analysis
  • Biochemical assays
  • Functional experiments

Main Results:

  • The forkhead-associated domain of Nbs1 directly interacts with INTS3.
  • This interaction is phosphorylation-dependent, specifically involving Threonine 592 and Serine 590 of INTS3.
  • A model for MRN complex recruitment to DSBs via INTS3 is proposed.

Conclusions:

  • INTS3 binding to Nbs1 is a critical step in recruiting the MRN complex to DNA damage sites.
  • Phosphorylation of INTS3 regulates its interaction with Nbs1, impacting DSB repair pathways.
Keywords:
DNA repairINTS3MRN complexNbs1SOSS complexhSSB1

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