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Related Concept Videos

Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

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Updated: Jun 8, 2026

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry
08:21

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry

Published on: September 1, 2019

Targeting hypoxic cells through the DNA damage response.

Monica Olcina1, Philip S Lecane, Ester M Hammond

  • 1The Cancer Research UK/MRC Gray Institute for Radiation Oncology and Biology, The University of Oxford, United Kingdom.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 30, 2010
PubMed
Summary
This summary is machine-generated.

Hypoxia causes replication stress, activating DNA damage responses distinct from those caused by DNA damage. Targeting these pathways, especially in reoxygenation, offers potential therapeutic strategies for hypoxic tumors.

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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

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Hypoxia is prevalent in solid tumors, influencing tumor progression and treatment resistance.
  • Tumor reoxygenation, a dynamic process, further complicates cellular responses to hypoxia.
  • Understanding the DNA damage response (DDR) under hypoxia is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the DNA damage response (DDR) initiated by hypoxia-induced replication arrest.
  • To elucidate the distinct mechanisms of hypoxia-induced DDR compared to classical DNA damaging agents.
  • To identify potential therapeutic targets within the hypoxia-induced DDR pathways.

Main Methods:

  • DNA fiber analysis to assess replication fork dynamics.
  • Evaluation of nucleotide levels during hypoxic conditions.
  • Assessment of DNA damage response signaling pathways, including ATR, ATM, and p53.
  • Analysis of the impact of hypoxia and reoxygenation on DNA repair components.

Main Results:

  • Hypoxia-induced replication arrest affects both initiation and elongation, correlating with decreased nucleotide pools.
  • The hypoxia-induced DDR is characterized by a lack of detectable DNA damage and repressed DNA repair.
  • Key DDR components like ATR, ATM, Chk1, and PARP are critical for survival under hypoxia/reoxygenation.
  • Phosphorylation of H2AX in endothelial cells under moderate hypoxia suggests a role in proliferation and angiogenesis.

Conclusions:

  • The hypoxia-induced DDR aims to induce apoptosis or preserve replication fork integrity for potential reoxygenation.
  • Hypoxic and reoxygenating tumor cells are sensitive to the inhibition of specific DDR components.
  • Targeting hypoxia-induced p53 signaling or H2AX phosphorylation presents promising therapeutic avenues for hypoxic tumors.