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Related Concept Videos

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

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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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.
There are several types of targeted therapies against specific...

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Author Correction: Polλ promotes microhomology-mediated end-joining.

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Related Experiment Video

Updated: May 16, 2026

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

Predicting enhanced cell killing through PARP inhibition.

Julie K Horton1, Samuel H Wilson

  • 1Laboratory of Structural Biology, National Institute of Environmental Health Sciences, 111 T.W. Alexander Dr., MD F1-12, Research Triangle Park, NC 27709, USA.

Molecular Cancer Research : MCR
|November 30, 2012
PubMed
Summary

Poly(ADP-ribose) polymerase (PARP) inhibitors enhance chemotherapy. Combining 4-amino-1,8-naphthalimide (4-AN) with temozolomide dramatically increases cancer cell death, unlike other DNA-damaging agents.

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Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
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Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

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Last Updated: May 16, 2026

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells
15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Poly(ADP-ribose) polymerase (PARP) inhibitors are investigated for cancer chemotherapy.
  • The base excision repair (BER) pathway repairs DNA damage, involving intermediates processed by enzymes like pol β.
  • PARP-1 activation by DNA repair intermediates is crucial for efficient repair.

Purpose of the Study:

  • To evaluate the efficacy of combining a PARP inhibitor, 4-amino-1,8-naphthalimide (4-AN), with DNA-damaging agents.
  • To analyze the potential for enhanced cytotoxicity through this combination therapy.
  • To understand the role of specific DNA repair pathways in mediating sensitization.

Main Methods:

  • Experiments were conducted using mouse fibroblasts.
  • The study utilized the PARP inhibitor 4-amino-1,8-naphthalimide (4-AN).
  • Cytotoxicity was assessed by combining 4-AN with various DNA-damaging agents, including temozolomide and agents causing oxidative damage.

Main Results:

  • Combining 4-AN with the methylating agent temozolomide resulted in extreme sensitization and significantly enhanced cytotoxicity.
  • In contrast, combining 4-AN with agents causing oxidative DNA damage, repaired by bifunctional glycosylase-initiated BER, showed only weak sensitization.
  • Minimal sensitization was observed when 4-AN was combined with other DNA-damaging agents repaired by different DNA repair pathways.

Conclusions:

  • The combination of PARP inhibitors with specific DNA-damaging agents, like temozolomide, can dramatically increase cancer cell killing.
  • The effectiveness of PARP inhibitor sensitization is dependent on the specific DNA repair pathway targeted by the chemotherapeutic agent.
  • These findings have significant implications for the strategic application of PARP inhibitors in cancer chemotherapy regimens.