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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...
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.
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

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Nucleotide Excision Repair01:08

Nucleotide Excision Repair

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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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Published on: August 21, 2021

DNA-damage response control of E2F7 and E2F8.

L Panagiotis Zalmas1, Xiujie Zhao, Anne L Graham

  • 1Laboratory of Cancer Biology, Medical Sciences Division, John Radcliffe Hospital, University of Oxford, Oxon, Oxford OX3 9DU, UK.

EMBO Reports
|January 19, 2008
PubMed
Summary

Newly discovered E2F7 and E2F8 proteins regulate the DNA-damage response. These E2F subunits repress E2F target genes, impacting cell-cycle progression after DNA damage.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The DNA-damage response (DDR) is crucial for maintaining genomic stability.
  • E2F transcription factors play key roles in cell-cycle regulation and DDR.
  • E2F7 and E2F8 are recently identified E2F family members with less understood functions.

Purpose of the Study:

  • To investigate the role of E2F7 and E2F8 in the DNA-damage response.
  • To elucidate the mechanism by which E2F7 and E2F8 influence DDR.
  • To determine the relationship between E2F7, E2F8, and other E2F factors, such as E2F1.

Main Methods:

  • Treatment of cells with DNA-damaging agents.
  • Analysis of E2F7 and E2F8 gene induction and protein expression.
  • Chromatin immunoprecipitation assays to assess E2F7/E2F8 binding to target gene promoters.
  • Quantitative real-time PCR and Western blotting to measure gene and protein expression levels.
  • Depletion studies using siRNA to evaluate the functional impact of E2F7 and E2F8.

Main Results:

  • E2F7 and E2F8 are induced upon DNA damage.
  • E2F7 and E2F8 bind to the promoters of E2F-responsive genes, including E2F1.
  • E2F7 and E2F8 repress the expression of E2F target genes, notably E2F1.
  • Depletion of E2F7 or E2F8 impairs DNA-damage-induced cell-cycle arrest.
  • E2F7 and E2F8 act upstream of E2F1 in the DDR pathway.

Conclusions:

  • E2F7 and E2F8 are critical regulators of the DNA-damage response.
  • These factors function upstream of E2F1 to control cell-cycle progression following DNA damage.
  • E2F7 and E2F8 are essential components that dictate the outcome of the DDR.