p53 Binds Single-Stranded DNA Ends and Catalyzes DNA Renaturation and Strand Transfer

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 1; pp. 413 - 417
• Main Authors: Bakalkin, Georgy, Yakovleva, Tatjana, Selivanova, Galina, Magnusson, Kristinn P., Szekely, Laszlo, Kiseleva, Elena, Klein, George, Terenius, Lars, Wiman, Klas G.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 04.01.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Antibodies; Base Sequence; Biochemistry; Biological and medical sciences; Deoxyribonucleic acid; DNA; DNA damage; DNA Repair; DNA, Single-Stranded - metabolism; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gels; Humans; In Vitro Techniques; Microscopy, Electron; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Molecules; Mutagenesis. Repair; Nucleic Acid Renaturation; Oligodeoxyribonucleotides - chemistry; Oligonucleotides; Oncogenes; Plasmids; Proteins; Recombinant Proteins; Single stranded DNA; Tumor Suppressor Protein p53 - metabolism; Tumors; Protein p53; Molecular hybridization; Binding capacity; Structure activity relation; Single stranded DNA; Recombinant protein; Repair; In vitro; Tumor suppressor gene
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.1.413

The p53 tumor-suppressor protein has previously been shown to bind double-stranded and single-stranded DNA. We report that the p53 protein can bind single-stranded DNA ends and catalyze DNA renaturation and DNA strand transfer. Both a bacterially expressed wild-type p53 protein and a glutathione S-transferase-wild-type p53 fusion protein catalyzed renaturation of different short (25- to 76-nt) complementary single-stranded DNA fragments and promoted strand transfer between short (36-bp) duplex DNA and complementary single-stranded DNA. Mutant p53 fusion proteins carrying amino acid substitutions Glu-213, Ile-237, or Tyr-238, derived from mutant p53 genes of Burkitt lymphomas, failed to catalyze these reactions. Wild-type p53 had significantly higher binding affinity for short (36- to 76-nt) than for longer (≥ 462-nt) single-stranded DNA fragments in an electrophoretic mobility-shift assay. Moreover, electron microscopy showed that p53 preferentially binds single-stranded DNA ends. Binding of DNA ends to p53 oligomers may allow alignment of complementary strands. These findings suggest that p53 may play a direct role in the repair of DNA breaks, including the joining of complementary single-stranded DNA ends.