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How cells activate ATR

Akiko Kumagai1, William G Dunphy

  • 1Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.

Cell Cycle (Georgetown, Tex.)
|June 9, 2006
PubMed

Insights

TopBP1 activates ATR kinase, a key protein in DNA damage response. This activation occurs when ATR interacts with TopBP1 at sites of DNA replication stress and damage, explaining how DNA damage triggers cell signaling.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • ATR kinase is essential for DNA damage and replication checkpoint control.
  • The precise mechanism of ATR kinase activation during cellular stress remained unclear.

Purpose of the Study:

  • To elucidate the mechanism by which ATR kinase activity is initiated during DNA damage and replication stress responses.

Main Methods:

  • The study builds upon previous findings identifying TopBP1 as a crucial protein in DNA replication and checkpoint control.
  • Investigated the interaction between ATR and TopBP1 at sites of DNA damage.

Main Results:

  • TopBP1 acts as an activator of ATR kinase.
  • TopBP1's accumulation at sites of replicative stress and DNA damage facilitates ATR activation.
  • ATR activation is triggered by its interaction with TopBP1 at stalled replication forks and DNA damage sites.

Conclusions:

  • The interaction between ATR and TopBP1 at DNA damage sites explains the activation of ATR-dependent signaling pathways.
  • This mechanism clarifies how aberrant DNA structures initiate ATR-mediated cellular responses.

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