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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.
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
The Cell Cycle Control System02:11

The Cell Cycle Control System

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
Replication in Eukaryotes01:29

Replication in Eukaryotes

In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...

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Related Experiment Video

Updated: Jul 14, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

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Published on: September 28, 2012

E2F4 function in G2: maintaining G2-arrest to prevent mitotic entry with damaged DNA.

Dragos Plesca1, Meredith E Crosby, Damodar Gupta

  • 1Department of Cancer Biology, The Lerner Research Institute, Cleveland, Ohio 44195, USA.

Cell Cycle (Georgetown, Tex.)
|May 18, 2007
PubMed
Summary

E2F4 protein is crucial for maintaining G2 cell cycle arrest after DNA damage, preventing genomic instability. Its nuclear translocation downregulates mitotic genes, promoting a G0-like state and enhancing cell survival.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Mammalian cells employ checkpoint mechanisms to arrest the cell cycle in response to DNA damage.
  • The G2 phase checkpoint delays mitotic progression, ensuring genomic integrity under genotoxic stress.
  • Cyclin B1/Cdk1 complexes regulate entry into mitosis, while p130 and Rb-dependent genes are vital for stable G2 arrest.

Purpose of the Study:

  • To review recent findings on G2 phase checkpoint activation and maintenance.
  • To highlight the specific role of E2F4 in the stable G2 arrest.
  • To discuss the molecular mechanisms underlying E2F4's function in DNA damage response.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of E2F4's interaction with p130.
  • Discussion of genotoxic stress-induced changes in E2F4 levels and localization.
  • Reference to comet assays, caspase activation, and DNA content analysis.

Main Results:

  • E2F4, upon interacting with p130, translocates to the nucleus and is key for stable G2 arrest.
  • Increased nuclear E2F4 downregulates mitotic genes, inducing a G0-like state.
  • E2F4 depletion enhances DNA double-strand breaks and leads to cell death via caspase activation and reduced survival.

Conclusions:

  • E2F4 plays a critical role in maintaining G2 arrest following DNA damage.
  • Nuclear E2F4 acts as a tumor suppressor by preventing genomic instability and promoting cell death in damaged cells.
  • Understanding E2F4's function provides insights into cancer prevention and therapy.