DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis.

Abstract

Mutations of SRY are the cause of 46,XY complete pure gonadal dysgenesis (PGD) in 10-15% of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model. DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C mutation, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA. In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY complete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity.

• Authors: Irene Sánchez-Moreno, Patricia Canto, Patricia Munguía, Mario Bermúdez de León, Bulmaro Cisneros, Felipe Vilchis, Edgardo Reyes, Juan Pablo Méndez
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 299 Issue 2 Pg. 212-8 (Feb 27 2009) ISSN: 0303-7207 [Print] Ireland
• PMID: 19007850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mutant Proteins
• SRY protein, human
• Sex-Determining Region Y Protein
• DNA

Topics

• Base Sequence
• Computational Biology
• DNA (metabolism)
• DNA Mutational Analysis
• Gonadal Dysgenesis, 46,XY (metabolism)
• Humans
• Models, Molecular
• Molecular Sequence Data
• Mutant Proteins (genetics, metabolism)
• Protein Binding
• Sex-Determining Region Y Protein (genetics, metabolism)