Related Experiment Video

Updated: Jul 5, 2026

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures
08:41

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures

Published on: December 27, 2024

Transgenic expression of E2F3a causes DNA damage leading to ATM-dependent apoptosis

Q X Paulson1, R V Pusapati, S Hong

  • 1Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957, USA.

Oncogene
|May 13, 2008
PubMed

Insights

Overexpression of E2F3a causes DNA damage and activates the DNA-damage response (DDR). The ataxia telangiectasia mutated (ATM) pathway suppresses E2F3a-induced tumors by promoting apoptosis, highlighting its role in cancer suppression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Early-stage human tumors often show DNA-damage response (DDR) markers, like activated ataxia telangiectasia mutated (ATM) kinase.
  • This suggests DNA damage accumulation during carcinogenesis and a potential cancer-suppressive role for the ATM-dependent DDR.
  • E2F3a, a transcription factor critical for cell proliferation, is amplified in some human cancers.

Purpose of the Study:

  • To investigate the role of E2F3a in DNA damage and the subsequent DDR.
  • To determine the involvement of ATM in E2F3a-induced apoptosis and tumor suppression.

Main Methods:

  • Utilized transgenic mice expressing E2F3a under a keratin 5 (K5) promoter to study DDR markers in hyperplastic epidermis.
  • Assessed DNA breaks in primary keratinocytes from K5-E2F3a mice and human fibroblasts.
  • Examined the effect of ATM absence and caffeine (ATM/ATR inhibitor) on E2F3a-induced apoptosis and skin tumor development.

Main Results:

  • K5-E2F3a transgenic mice exhibited activated ATM and other DDR markers in hyperplastic epidermis.
  • E2F3a overexpression led to increased DNA breaks in mouse keratinocytes and human fibroblasts, with replication blockage inhibiting this effect.
  • ATM deficiency impaired E2F3a-induced apoptosis, and caffeine treatment accelerated skin tumor development in K5-E2F3a mice.

Conclusions:

  • Deregulated E2F3a expression induces DNA damage under physiological conditions.
  • The ATM-dependent DDR is crucial for initiating apoptosis and suppressing tumor formation in response to E2F3a overexpression.

More Related Videos

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics12:28

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

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...
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...
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...
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...