Nucleophosmin redistribution following heat shock: A role in heat-induced radiosensitization

Robert P. Vanderwaal, Leonard B. Maggi, Jason D. Weber, Clayton R. Hunt, Joseph L. Roti Roti

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)6454-6462
Number of pages9
JournalCancer research
Volume69
Issue number16
DOIs
StatePublished - Aug 15 2009

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