Analysis of the binding of p53 to DNAs containing mismatched and bulged bases.
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.
Degtyareva
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Lineberger Comprehensive Cancer Center and the Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA.
Subramanian
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Griffith
J D
JD
D020137:Base Pair Mismatch; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C098790:MSH6 protein, S cerevisiae; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA; D051718:MutS Homolog 2 Protein