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

David Shechter, Vincenzo Costanzo, Jean Gautier

Research output: Contribution to journalReview article

157 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)901-908
Number of pages8
JournalDNA Repair
Volume3
Issue number8-9
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

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Keywords

  • ATR
  • Checkpoint
  • DNA replication
  • RPA
  • Single-stranded DNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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