Interaction of normal and mutant SRY proteins with DNA.

Abstract

In mammals, sex determination is caused by the Y-chromosome gene SRY. The DNA-binding domain of human SRY protein is similar to those of the chromatin protein HMG1. Like HMG1, SRY binds to kinked DNA structures, and bends linear DNA sharply upon binding. We analysed the biochemical properties of mutant SRY proteins from five patients with complete gonadal dysgenesis: two bind and bend DNA almost normally, two bind inefficiently but bend DNA normally, and one binds DNA with almost normal affinity but produces a different angle. The mutations with moderate effect on complex formation can be transmitted to progeny, the ones with severe effects on either binding or bending are de novo. The angle induced by SRY depends on the exact DNA sequence, thus discriminating different target sites. We suggest that the exact spatial arrangement of the nucleoprotein complex organized by SRY in chromatin is essential for the expression of genes involved in testis differentiation.

• Authors: R Rimini, A Pontiggia, F Spada, S Ferrari, V R Harley, P N Goodfellow, M E Bianchi
• Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences (Philos Trans R Soc Lond B Biol Sci) Vol. 350 Issue 1333 Pg. 215-20 (Nov 29 1995) ISSN: 0962-8436 [Print] England
• PMID: 8570684 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromatin
• DNA-Binding Proteins
• Nuclear Proteins
• SRY protein, human
• Sex-Determining Region Y Protein
• Transcription Factors
• DNA

Topics

• Base Sequence
• Chromatin (genetics)
• DNA (analysis)
• DNA-Binding Proteins (genetics)
• Enhancer Elements, Genetic (genetics)
• Gene Expression (physiology)
• Humans
• Male
• Mutation (genetics)
• Nuclear Proteins
• Nucleic Acid Conformation
• Sex Determination Analysis
• Sex-Determining Region Y Protein
• Transcription Factors
• Y Chromosome (genetics)