Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1

Isabel M Pires, Zuzana Bencokova, Chris McGurk, Ester M Hammond

Research output: Contribution to journalArticlepeer-review

Abstract

Severe hypoxia has been demonstrated to induce a replication arrest which is associated with decreased levels of nucleotides. Chk1 is rapidly phosphorylated in response to severe hypoxia and in turn deactivates TLK1 through phosphorylation. Loss of Chk1 has been shown to sensitize cells to hypoxia/reoxygenation. After short (acute) exposure to hypoxia this is due to an increased rate of reoxygenation-induced replication restart and subsequent p53-dependent apoptosis. After longer (chronic) exposure to hypoxia S phase cells do not undergo reoxygenation-induced replication restart. Cells exposed to these levels of hypoxia however are sensitive to loss of Chk1. This suggests a new role for Chk1 in the cell cycle response to reoxygenation.

Original languageEnglish
Pages (from-to)2502-2507
Number of pages6
JournalCell cycle (Georgetown, Tex.)
Volume9
Issue number13
DOIs
Publication statusPublished - 1 Jul 2010

Keywords

  • cell Hypoxia/drug effects
  • checkpoint Kinase 1
  • DNA Damage
  • DNA Repair/drug effects
  • DNA Replication/drug effects
  • Models, Biological
  • Oxygen/pharmacology
  • Phosphorylation/drug effects
  • Protein Kinases/metabolism
  • Protein Serine-Threonine Kinases/metabolism
  • Rad51 Recombinase/metabolism
  • Signal Transduction/drug effects

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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