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

DNA Repair (Amst). Aug-Sep 2004;3(8-9):901-8. doi: 10.1016/j.dnarep.2004.03.020.

Abstract

The nuclear protein kinase ATR controls S-phase progression in response to DNA damage and replication fork stalling, including damage caused by ultraviolet irradiation, hyperoxia, and replication inhibitors like aphidicolin and hydroxyurea. ATR activation and substrate specificity require the presence of adapter and mediator molecules, ultimately resulting in the downstream inhibition of the S-phase kinases that function to initiate DNA replication at origins of replication. The data reviewed strongly support the hypothesis that ATR is activated in response to persistent RPA-bound single-stranded DNA, a common intermediate of unstressed and damaged DNA replication and metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Aphidicolin / metabolism
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • DNA / genetics*
  • DNA Damage
  • DNA Replication
  • DNA, Single-Stranded / genetics
  • Humans
  • Hydroxyurea / metabolism
  • Mice
  • Models, Biological
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • S Phase
  • Saccharomyces cerevisiae / metabolism
  • Signal Transduction*
  • Ultraviolet Rays

Substances

  • Cell Cycle Proteins
  • DNA, Single-Stranded
  • Aphidicolin
  • DNA
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • Hydroxyurea