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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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Surviving the breakup: the DNA damage checkpoint

Jacob C Harrison1, James E Haber

  • 1Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02445, USA. harrison@brandeis.edu

Annual Review of Genetics
|June 30, 2006
PubMed

Insights

Cells activate the DNA damage checkpoint to arrest the cell cycle, allowing DNA repair and maintaining genomic stability. This process involves kinases like ATM and ATR, and chromatin modifications, with distinct recovery and adaptation mechanisms.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Cells possess a DNA damage checkpoint to respond to chromosomal double-strand breaks.
  • This checkpoint induces cell cycle arrest, facilitating DNA repair and preventing genomic instability.
  • Key players include ATM and ATR kinases, crucial for checkpoint activation and effector signaling.

Purpose of the Study:

  • To elucidate the molecular mechanisms of DNA damage checkpoint activation.
  • To understand the role of chromatin modification in checkpoint processes.
  • To differentiate between checkpoint recovery and adaptation mechanisms.

Main Methods:

  • Focus on molecular mechanisms of checkpoint activation.
  • Investigating recruitment of ATM and ATR kinases to damaged DNA.
  • Analyzing chromatin modifications during checkpoint response.

Main Results:

  • Checkpoint activation involves recruitment of ATM and ATR kinases to damaged DNA sites.
  • Chromatin modification is integral to checkpoint activation and maintenance.
  • Distinct processes of recovery (inactivation post-repair) and adaptation (re-entry with unrepairable damage) exist.

Conclusions:

  • The DNA damage checkpoint is essential for genomic stability.
  • Understanding kinase recruitment and chromatin modification provides insight into checkpoint control.
  • Cellular responses to DNA damage include regulated inactivation and controlled re-entry.

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