title: UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML.
abstract: 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.
authors.affiliation: Laboratory of Human Carcinogenesis, CCR, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA.
authors.forename: Hasan
authors.initials: H
authors.lastname: Seker
authors.forename: Carlos
authors.initials: C
authors.lastname: Rubbi
authors.forename: Steven P
authors.initials: SP
authors.lastname: Linke
authors.forename: Elise D
authors.initials: ED
authors.lastname: Bowman
authors.forename: Susan
authors.initials: S
authors.lastname: Garfield
authors.forename: Laura
authors.initials: L
authors.lastname: Hansen
authors.forename: Katherine L B
authors.initials: KL
authors.lastname: Borden
authors.forename: Jo
authors.initials: J
authors.lastname: Milner
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D002460:Cell Line; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D021381:Protein Transport / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D014466:Ultraviolet Rays
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004247:DNA