title: Loss of HSF1 results in defective radiation-induced G(2) arrest and DNA repair.
abstract: HSF1 is a transcription factor that plays a key role in the response to heat stress and was previously shown by us to also be essential for importation of p53 into the nucleus. Here we extend these studies and show that loss of HSF1 renders cells more sensitive to killing by ionizing radiation. Cells that lack a functional HSF1 were unable to arrest in G(2) after exposure to ionizing radiation, suggesting that HSF1 activity was essential for activation of this cell cycle checkpoint. In addition, cells with no HSF1 showed a reduced capacity to repair radiation-induced double-stranded DNA breaks. We found that in these cells 53BP1 did not accumulate at sites of DNA damage, suggesting that HSF1 was also essential for the functioning of this DNA damage mediator. Taken together our results indicate that HSF1 plays an important role in checkpoint activation and DNA repair and suggest that there is overlap between the heat stress response pathway and the pathway that responds to ionizing radiation.
authors.affiliation: Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Martinez
mesh_terms: D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics* / Q000528:radiation effects*; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D014157:Transcription Factors; D000071857:Tumor Suppressor p53-Binding Protein 1