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.
Centre de Recherche de Biochimie Macromoléculaire, CNRS UPR 9008, INSERM U. 249, Montpellier, France.
F
F
Poulat
S
S
Soullier
C
C
Gozé
F
F
Heitz
B
B
Calas
P
P
Berta
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