Projects & Grants
|Interactions of wild type and mutant p53 proteins with damaged DNA and their roles in cellular response to anticancer chemotherapy
|doc. RNDr. Petr Pečinka, CSc.
|1/2007 - 12/2010
|Standardní grantový projekt GA AV
|Interactions of tumor suppressor protein p53 with DNA are crucial for its biological activities. It was suggested that not only the wild type (wt) p53 sequence-specific DNA binding, but also ability of both wt and mutant (mut) p53 to recognize DNA structure, are important for their characteristic functions. We propose to study wt and mut p53 interactions with damaged DNA, particularly DNA treated with antitumor drugs. These studies will be focused on (1) the ability of mutp53 to recognize specific DNA damage, (2) effects of DNA damage on the wt p53 sequence-specific DNA binding, and (3) influence of genotoxic substances on mut p53 binding to genomic DNA elements identified as its natural binding sites in vivo. Using biochemical and molecular-biological techniques, interactions of purified proteins with DNA in cell-free system will be investigated in the first stage, followed by studies of the influence of genotoxic agents on p53-DNA binding at the level of model cell lines.