Work

Nucleophosmin Redistribution following Heat Shock: A Role in Heat-Induced Radiosensitization

Year: 2009

Type: article

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 DSB repair. Also, these results suggest that NPM associates with nuclear matrix attachment region DNA in heat-shocked cells.

Source: Cancer Research

DOI: 10.1158/0008-5472.can-08-4896

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

Institutions: Washington University in St. Louis, Houston Methodist

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute