title: Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1.
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.
authors.affiliation: The Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, UK.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Pires
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Bencokova
authors.forename: Chris
authors.initials: C
authors.lastname: McGurk
authors.forename: Ester M
authors.initials: EM
authors.lastname: Hammond
mesh_terms: D015687:Cell Hypoxia / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D008954:Models, Biological; D010100:Oxygen / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D051135:Rad51 Recombinase; D010100:Oxygen