TY - JOUR
T1 - Nucleophosmin redistribution following heat shock
T2 - A role in heat-induced radiosensitization
AU - Vanderwaal, Robert P.
AU - Maggi, Leonard B.
AU - Weber, Jason D.
AU - Hunt, Clayton R.
AU - Roti Roti, Joseph L.
PY - 2009/8/15
Y1 - 2009/8/15
N2 - 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 DSBr epair. Also, these results suggest that NPM associates with nuclear matrix attachment region DNA in heat-shocked cells.
AB - 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 DSBr epair. Also, these results suggest that NPM associates with nuclear matrix attachment region DNA in heat-shocked cells.
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U2 - 10.1158/0008-5472.CAN-08-4896
DO - 10.1158/0008-5472.CAN-08-4896
M3 - Article
C2 - 19638589
AN - SCOPUS:69249127842
SN - 0008-5472
VL - 69
SP - 6454
EP - 6462
JO - Cancer research
JF - Cancer research
IS - 16
ER -