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The histone acetyltransferase CBP participates in regulating the DNA damage response through ATM after double-strand

Wafaa S Ramadan1,2, Samrein B M Ahmed3, Iman M Talaat1,2

  • 1Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.

Genome Biology
|April 8, 2025
PubMed
Abstract

Insights

The CREB-binding protein (CBP) stabilizes and activates ATM kinase following DNA damage. CBP

Area of Science:

  • Molecular Biology
  • Genomics
  • Biochemistry

Background:

  • Genomic stability relies on precise control of DNA damage response (DDR) pathways.
  • The Ataxia Telangiectasia Mutated (ATM) protein is central to DDR, but its activation pathway is not fully understood.
  • The role of CREB-binding protein (CBP), a histone acetyltransferase (HAT), in DDR and ATM activation requires further investigation.

Purpose of the Study:

  • To investigate the function of CREB-binding protein (CBP) in DNA damage response.
  • To elucidate the role of CBP in the activation pathway of ATM kinase.

Main Methods:

  • Studied the stabilization and recruitment of CBP at DNA double-strand break sites.
  • Assessed the acetylation of ATM by CBP and its effect on kinase activity.
  • Examined DNA double-strand break repair capabilities in CBP-deficient cells and cells with restored CBP HAT domain.

Main Results:

  • CBP is stabilized and recruited to DNA double-strand breaks upon DNA damage.
  • CBP acetylates ATM, promoting its kinase activity, which is crucial for DNA repair.
  • CBP deficiency impairs DNA double-strand break repair and increases sensitivity to genotoxic agents.
  • Restoration of CBP's HAT domain in deficient cells rescues DNA repair capacity.

Conclusions:

  • CBP is a key regulator of ATM activation and DNA double-strand break repair.
  • CBP's HAT domain is essential for efficient DNA repair.
  • CBP represents a potential therapeutic target for modulating cancer treatment responses.
Keywords:
ATMCBPDNA DSBsDNA repairHistone acetyltransferase

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