Nucleophosmin redistribution following heat shock: a role in heat-induced radiosensitization.
Cellular survival from radiation-induced DNA damage requires access to sites of damage for the assembly of repair complexes and the subsequent repair, particularly the repair of DNA double strand breaks (DSB). Hyperthermia causes changes in protein-protein/DNA interactions in the nucleus that block access to sites of DNA damage. Studies presented here indicate that the nucleolar protein, nucleophosmin (NPM), redistributes from the nucleolus following hyperthermia, increases its association with DNA, and blocks access to DNA DSBs. Reduction of NPM significantly reduces heat-induced radiosensitization, but reduced NPM level does not alter radiation sensitivity per se. NPM knockdown reduces heat-induced inhibition of DNA DSB repair. Also, these results suggest that NPM associates with nuclear matrix attachment region DNA in heat-shocked cells.
Vanderwaal
Robert P
RP
Department of Radiation Oncology, Washington University, St. Louis, Missouri 63108, USA.
Maggi
Leonard B
LB
Weber
Jason D
JD
Hunt
Clayton R
CR
Roti Roti
Joseph L
JL
D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D018869:Heat-Shock Response / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D034741:RNA, Small Interfering / Q000494:pharmacology; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014018:Tissue Distribution / Q000187:drug effects; D014407:Tumor Cells, Cultured
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D000090243:Nucleophosmin