Interaction with p53 enhances binding of cisplatin-modified DNA by high mobility group 1 protein

A nonhistone chromosomal protein, high mobility group (HMG) I, is ubiquitou s in higher eukaryotic cells and binds preferentially to cisplatin-modified DNA. HMG1 also functions as a coactivator of p53, a tumor suppressor prote in. We investigated physical interactions between HMG1 and p53 and the infl uence of p53 on the:ability of HMG1 to recognize damaged DNA. Using immunoc hemical coprecipitation, we observed binding of HMG1 and p53, Interaction b etween HMG1 and p53 required the HMG A box of HMG1 and amino acids 363-376 of p53. Cisplatin-modified DNA binding by HMG1 was significantly enhanced b y p53. An HMG1-specific antibody that recognized the A box of this protein also stimulated cisplatin-modified DNA binding. These data suggest that an interaction with either p53 or antibody may induce conformational change in the HMG1 A box that optimizes DNA binding by HMG1. Interaction of p53 with HMG1 after DNA damage may promote activation of specific HMG1 binding to d amaged DNA in vivo and provide a molecular link, between DNA damage and p53 -mediated DNA repair.