UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML.

Hasan Seker, Carlos Rubbi, Steven P Linke, Elise D Bowman, Susan Garfield, Laura Hansen, Katherine L B Borden, Jo Milner, Curtis C Harris

Laboratory of Human Carcinogenesis, CCR, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA.

Oncogene 2003 Mar 20

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The promyelocytic leukemia protein (PML) is a nuclear phosphoprotein that localizes to distinct domains in the nucleus, described as PML nuclear bodies (PML-NBs). Recent findings indicate that PML regulates the p53 response to oncogenic signals. Here, we define a p53-dependent role for PML in response to DNA damage. We exposed cells to ultraviolet light (UV-C) and imaged the nuclear distribution of PML, p53, and the BLM helicase by confocal microscopy. After DNA damage, PML partially relocated out of the PML-NBs, and colocalized with BLM and p53 at sites of DNA repair. In addition, using the isogenic HCT116 cell lines (p53+/+ and -/-), we show that the redistribution of PML was dependent on functional p53. Western analysis revealed that the level of PML protein remained unaltered after UV-C treatment. These results are consistent with the hypothesis that PML, in conjunction with p53 and BLM, contributes to the cellular response to UV-C-induced DNA damage and its repair.

Citation

Hasan Seker, Carlos Rubbi, Steven P Linke, Elise D Bowman, Susan Garfield, Laura Hansen, Katherine L B Borden, Jo Milner, Curtis C Harris. UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML. Oncogene. 2003 Mar 20;22(11):1620-8