Related Experiment Video

Updated: Aug 18, 2026

Study of the DNA Damage Checkpoint using Xenopus Egg Extracts
10:55

Study of the DNA Damage Checkpoint using Xenopus Egg Extracts

Published on: November 5, 2012

G2 damage checkpoints: what is the turn-on?

Matthew J O'Connell1, Karlene A Cimprich

  • 1Department of Oncological Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA. matthew.oconnell@mssm.edu

Journal of Cell Science
|December 24, 2004
PubMed

Insights

Cells activate DNA repair and cell-cycle checkpoints upon DNA damage. The p53-independent pathway, crucial in G2, uses ATR kinase signaling to halt cell division, preventing further damage.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Cells possess coordinated responses to DNA damage, involving DNA repair and cell-cycle checkpoints.
  • Checkpoint responses in human cells are categorized into p53-dependent and p53-independent pathways.
  • The p53-independent pathway is predominant in the G2 phase of the cell cycle.

Purpose of the Study:

  • To elucidate the mechanisms by which ATM and ATR kinases recognize DNA damage and activate the p53-independent checkpoint pathway.
  • To understand the role of single-stranded DNA in ATR activation.
  • To detail the signaling cascade leading to G2 arrest.

Main Methods:

  • Investigating the role of ATR and ATM kinases in DNA damage response.
  • Analyzing the involvement of single-stranded DNA (ssDNA) in checkpoint activation.
  • Studying the phosphorylation cascade involving ATR, Chk1, and Cdc2.

Main Results:

  • Single-stranded DNA is central to ATR activation, recruiting checkpoint protein complexes.
  • ATR phosphorylates Chk1, activating it to induce G2 arrest.
  • This pathway enforces a block to mitotic entry, allowing time for DNA repair.

Conclusions:

  • The ATR-Chk1 signaling pathway is a key component of the p53-independent DNA damage response in G2 phase.
  • Recognition of ssDNA by ATR is a critical step in initiating the checkpoint.
  • This mechanism ensures genomic stability by preventing cell division with damaged DNA.

More Related Videos

Temporal Tracking of Cell Cycle Progression Using Flow Cytometry without the Need for Synchronization08:52

Temporal Tracking of Cell Cycle Progression Using Flow Cytometry without the Need for Synchronization

Published on: August 16, 2015

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

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...
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...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
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 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...
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...