Description and functional implications of a novel mutation in the sex-determining gene SRY.
The sex-determining gene SRY was screened for molecular alteration in an XY sex-reversed female by single-strand conformation polymorphism (SSCP) technique. An A-to-G transition was detected which leads to an exchange of a tyrosine by a cysteine in the SRY protein. The affected tyrosine residue located at the C terminus of the DNA binding protein is evolutionarily strongly conserved among the members of the HMG box containing proteins. Using gel shift assay and peptide synthesis such a mutation is shown to abolish the SRY protein DNA binding ability. The involvement of this particular amino acid in the binding specificity is also discussed.
Poulat
F
F
Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 9008, INSERM U. 249, Montpellier, France.
Soullier
S
S
Gozé
C
C
Heitz
F
F
Calas
B
B
Berta
P
P
D000293:Adolescent; D000568:Amenorrhea / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000302:isolation & purification; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012732:Sex Determination Analysis; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors / Q000235:genetics; D014960:X Chromosome; D014998:Y Chromosome
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D004247:DNA