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Regulation of DNA replication by ATR: signaling in response to DNA intermediates

David Shechter1, Vincenzo Costanzo, Jean Gautier

  • 1Department of Genetics and Development, Hammer Health Sciences Center, Room 1620, Columbia University College of Physicians and Surgeons, 701 W. 168th Street, New York, NY 10032, USA. ds453@columbia.edu

DNA Repair
|July 29, 2004
PubMed

Insights

The nuclear protein kinase ATR regulates cell cycle progression by responding to DNA damage and stalled replication forks. ATR activation, crucial for DNA repair, is triggered by RPA-bound single-stranded DNA.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Genetics

Background:

  • The protein kinase ATR (Ataxia Telangiectasia and Rad3-related) is a key regulator of the DNA damage response.
  • ATR controls S-phase progression, preventing genomic instability when cells encounter DNA damage or replication stress.

Purpose of the Study:

  • To review the mechanisms of ATR activation and its role in maintaining genome stability.
  • To elucidate the molecular triggers for ATR activation during DNA replication and repair.

Main Methods:

  • Review of existing literature on ATR signaling pathways.
  • Analysis of data concerning DNA replication, DNA damage, and protein interactions.

Main Results:

  • ATR activation requires adapter and mediator molecules.
  • ATR activation leads to the inhibition of S-phase kinases, preventing DNA replication origin firing.
  • Persistent RPA-bound single-stranded DNA is identified as a key activator of ATR.

Conclusions:

  • ATR plays a critical role in cell cycle control following DNA damage and replication stress.
  • The findings support a model where ATR activation is a direct response to specific DNA structures arising during replication and repair.

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