title: The molecular basis of the undulated/Pax-1 mutation.
abstract: The murine paired box gene Pax-1 has been associated with the mouse developmental mutant undulated (un), which exhibits malformations in the vertebral column. In un mice, a point mutation leading to a Gly-Ser exchange in a conserved part of the paired domain of Pax-1 is present. Here we show that Pax-1 encodes a DNA-binding protein with transcriptional activating properties. The DNA-binding specificity of the Pax-1 protein has been extensively analyzed in gel shift assays, and in conjunction with binding interference experiments, a DNA-binding core motif was defined. Comparison of the DNA-binding properties of wild-type and un Pax-1 proteins demonstrates that the Gly-Ser replacement at position 15 within the paired domain dramatically decreases the DNA-binding affinity of the un Pax-1 protein and alters its DNA-binding specificity. These results decipher the molecular basis of the un mutation.
authors.affiliation: Max-Planck Institute for Biophysical Chemistry, Department of Molecular Cell Biology, Göttingen, Federal Republic of Germany.
authors.forename: G
authors.initials: G
authors.lastname: Chalepakis
authors.forename: R
authors.initials: R
authors.lastname: Fritsch
authors.forename: H
authors.initials: H
authors.lastname: Fickenscher
authors.forename: U
authors.initials: U
authors.lastname: Deutsch
authors.forename: M
authors.initials: M
authors.lastname: Goulding
authors.forename: P
authors.initials: P
authors.lastname: Gruss
mesh_terms: D000478:Alkylation; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D003196:Computer Graphics; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D051761:Paired Box Transcription Factors; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C070835:PAX1 transcription factor; D004247:DNA