title: The Myb oncogene product induces DNA-bending.
abstract: The nuclear oncogene v-myb and its cellular counterpart c-myb code for proteins that bind to DNA in a sequence specific manner and act as regulators of transcription. The Myb protein contains DNA binding and trans-regulatory domains which are important for its function. The DNA binding domain of Myb protein has been shown to contain three imperfectly conserved repeats of 50-52 amino acids that constitute the amino terminal end. In this communication, we show that Myb protein induces conformational change in DNA after protein-DNA complex formation. Circular permutation assays indicate that Myb protein induces DNA bending at the site of binding. Phasing analysis confirm the DNA bending and allowed the detection of relative orientation of bend. Myb proteins which comprise only DNA-binding domains either with three repeats or two repeats also bend DNA in the same orientation as the larger proteins with both DNA-binding and transactivating domains. However, the transactivating region seems to influence the magnitude of bend angle. We used molecular modeling to analyse the structure of Myb-DNA complex formation resulting in the bending of DNA. Data presented here show that Myb protein, like other transcriptional regulators, bends DNA upon binding allowing the interaction of regulatory elements.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA.
authors.forename: P
authors.initials: P
authors.lastname: Saikumar
authors.forename: J L
authors.initials: JL
authors.lastname: Gabriel
authors.forename: E P
authors.initials: EP
authors.lastname: Reddy
mesh_terms: D001483:Base Sequence; D004268:DNA-Binding Proteins; D004586:Electrophoresis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators