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Updated: Feb 25, 2026

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
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Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

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Chaperoning the DNA damage response

Travis H Stracker1

  • 1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Spain.

The FEBS Journal
|August 8, 2017
PubMed

Insights

Heat shock protein 90 alpha (HSP90α) is crucial for the stability of DNA repair proteins Nibrin (NBN) and ATM kinase. Inhibiting HSP90 impairs DNA damage response, explaining how HSP90 inhibitors enhance chemotherapy effectiveness.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • The MRE11-RAD50-NBN (MRN) complex plays a critical role in DNA double-strand break repair.
  • ATM kinase is a key regulator of the cellular response to DNA damage.
  • Heat shock protein 90 alpha (HSP90α) is a molecular chaperone involved in stabilizing client proteins.

Purpose of the Study:

  • To investigate the role of HSP90α in the stability and function of the NBN component of the MRN complex and ATM kinase.
  • To elucidate the impact of HSP90 inhibition on DNA damage response pathways.
  • To explain the chemosensitizing effects of HSP90 inhibitors.

Main Methods:

  • Identifying NBN and ATM as HSP90α clients.
  • Assessing the stability of NBN and ATM upon HSP90 inhibition.
  • Evaluating the DNA damage response in cells treated with HSP90 inhibitors.

Main Results:

  • NBN and ATM were confirmed as client proteins of HSP90α.
  • Inhibition of HSP90α led to decreased stability of both NBN and ATM.
  • Impaired DNA damage response was observed following HSP90 inhibition.

Conclusions:

  • HSP90α is essential for maintaining the stability of NBN and ATM.
  • HSP90α activity is critical for an effective DNA damage response.
  • The findings provide mechanistic insight into the chemosensitizing effects of HSP90 inhibitors in cancer therapy.

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