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Updated: Dec 19, 2025

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

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DNA damage checkpoint kinases in cancer

Hannah L Smith1, Harriet Southgate2, Deborah A Tweddle2

  • 1Newcastle Centre for Cancer Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.

Expert Reviews in Molecular Medicine
|June 9, 2020
PubMed

Insights

The DNA damage response (DDR) pathway protects cells from DNA damage. This review explores targeting ATM-CHK2-p53 and ATR-CHK1-Wee1 pathways for cancer therapy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The DNA damage response (DDR) pathway is a crucial network of signaling and repair pathways that prevents replication of DNA damage.
  • Cell cycle checkpoints, including G1, S, and G2/M, are regulated by specific DDR pathways like ATM-CHK2-p53 and ATR-CHK1-Wee1.
  • Loss of G1 checkpoint control, often due to TP53 or ATM mutations, is frequent in cancer, highlighting the importance of targeting S/G2 checkpoints.

Purpose of the Study:

  • This review focuses on the ATM-CHK2-p53-p21 and ATR-CHK1-WEE1 pathways within the DDR network.
  • It examines ongoing therapeutic strategies aimed at targeting these specific DDR pathways for patient benefit.

Main Methods:

  • The review synthesizes current knowledge on the ATM-CHK2-p53-p21 and ATR-CHK1-WEE1 pathways.
  • It discusses the rationale and ongoing efforts in targeting these pathways for cancer treatment.

Main Results:

  • Dysregulation of G1 checkpoint control is a common hallmark of cancer.
  • The ATM-CHK2-p53 and ATR-CHK1-WEE1 pathways play critical roles in maintaining genomic integrity by controlling cell cycle progression.
  • Targeting these S/G2 checkpoints offers a promising therapeutic avenue.

Conclusions:

  • Understanding the intricacies of the ATM-CHK2-p53-p21 and ATR-CHK1-WEE1 pathways is vital for developing effective cancer therapies.
  • Targeting these DDR pathways represents a significant area of ongoing research with the potential to improve patient outcomes.
Keywords:
ATMATRCDK1CDK2CHK1CHK2DNA damage responseWEE1cell cyclep53

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