Analysis of the Binding of p53 to DNAs Containing Mismatched and Bulged Bases

• Published in: The Journal of biological chemistry Vol. 276; no. 12; pp. 8778 - 8784
• Main Authors: Degtyareva, Natalya, Subramanian, Deepa, Griffith, Jack D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.03.2001; American Society for Biochemistry and Molecular Biology
• Subjects: Base Pair Mismatch; Base Sequence; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA-Binding Proteins; Fungal Proteins - metabolism; hMSH2 protein; hMSH6 protein; Molecular Sequence Data; MutS Homolog 2 Protein; nucleotides; Protein Binding; Proto-Oncogene Proteins - metabolism; Saccharomyces cerevisiae Proteins; Sequence Homology, Nucleic Acid; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M006795200

The tumor suppressor protein p53 modulates cellular response to DNA damage by a variety of mechanisms that may include direct recognition of some forms of primary DNA damage. Linear 49-base pair duplex DNAs were constructed containing all possible single-base mismatches as well as a 3-cytosine bulge. Filter binding and gel retardation assays revealed that the affinity of p53 for a number of these lesions was equal to or greater than that of the human mismatch repair complex, hMSH2-hMSH6, under the same binding conditions. However, other mismatches including G/T, which is bound strongly by hMSH2-hMSH6, were poorly recognized by p53. The general order of affinity of p53 was greatest for a 3-cytosine bulge followed by A/G and C/C mismatches, then C/T and G/T mismatches, and finally all the other mismatches.