title: Checking in on hypoxia/reoxygenation.
abstract: Hypoxia/reoxygenation is a physiological stress that activates the DNA damage pathway. Significantly, this pathway is initiated during hypoxia, in the absence of detectable DNA damage. Our most recent study determined that during hypoxia, Chk 2 is phosphorylated in an ATM-dependent manner. In addition to this finding, we found that components of the MRN complex were not required for Chk 2 phosphorylation during hypoxia/reoxygenation. Once activated, Chk 2 initiates a signaling cascade, which induces a cell cycle arrest in the G2 phase. Loss of the Chk 2-mediated arrest correlated with an increase in sensitivity to hypoxia/reoxygenation. In contrast, loss of a p53-mediated reoxygenation-induced G1 arrest does not correlate with increased sensitivity to hypoxia/reoxygenation.
authors.affiliation: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Center for Clinical Sciences Research, Stanford University, Stanford, California 94303-5152, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Freiberg
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Krieg
authors.forename: Amato J
authors.initials: AJ
authors.lastname: Giaccia
authors.forename: Ester M
authors.initials: EM
authors.lastname: Hammond
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D010100:Oxygen