Mechanisms of DNA binding by tumor suppressor protein p53

DNA binding by the tumor suppressor protein p53 is crucial for its biological functions, and the recognition of specific DNA elements by p53 is given not only by nucleotide sequence of the binding site, but also by local and global DNA conformation, its chemical modification and by DNA stretches flanking the binding site. The DCMBO has contributed considerably to these findings through complex studies of p53 interactions with large topologically distinct DNA substrates which mimic some features of DNA in vivo better than isolated short target sequences (used in most of other studies).

V. Brazda, E.B. Jagelska, M. Fojta, and E. Palecek, Searching for target sequences by p53 protein is influenced by DNA length. Biochemical and Biophysical Research Communications 341, 470-477, 2006.

E.B. Jagelska, V. Brazda, P. Pecinka, E. Palecek, and M. Fojta, DNA topology influences p53 sequence-specific DNA binding through structural transitions within the target sites. Biochemical Journal 412, 57-63, 2008.

H. Pivonkova, M. Brazdova, J. Kasparkova, V. Brabec, and M. Fojta, Recognition of cisplatin-damaged DNA by p53 protein: Critical role of the p53 C-terminal domain. Biochemical and Biophysical Research Communications 339, 477-484, 2006.

H. Pivonkova, P. Pecinka, P. Ceskova, and M. Fojta, DNA modification with cisplatin affects sequence-specific DNA binding of p53 and p73 proteins in a target site-dependent manner.Febs Journal 273, 4693-4706,2006.

M. Brazdova, T. Quante, L. Togel, K. Walter, C. Loscher, V. Tichy, L. Cincarova, W. Deppert, and G.V. Tolstonog, Modulation of gene expression in U251 glioblastoma cells by binding of mutant p53 R273H to intronic and intergenic sequences. Nucleic Acids Research 37, 1486-1500, 2009.