title: p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches.
abstract: Insertion/deletion (IDL) mismatches in DNA are lesions consisting of extra bases on one strand. Here, the binding of p53 and its 14 kDa C-terminal domain to DNAs containing one or three 3-cytosine IDL mismatches was examined. Electron microscopy showed that both p53 forms bound predominantly as tetramers at the lesions while single-stranded binding proteins did not bind. Gel retardation assays showed that p53 formed highly stable complexes when the DNA contained the IDL mismatches, but only unstable complexes when the DNA lacked lesions (but did contain free ends). The highly stable complexes had a half-life of > 2 hr, suggesting that upon encountering lesions, p53 may recruit other proteins to the site, providing a signal for DNA damage.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill 27599-7295, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Elenbaas
authors.forename: A
authors.initials: A
authors.lastname: Levine
authors.forename: J
authors.initials: J
authors.lastname: Griffith
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D004249:DNA Damage; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure; D017384:Sequence Deletion; D013698:Templates, Genetic; D016159:Tumor Suppressor Protein p53 / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA