Interaction of normal and mutant SRY proteins with DNA

R. Rimini, A. Pontiggia, F. Spada, S. Ferrari, V. R. Harley, P. N. Goodfellow, M. E. Bianchi

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)215-220
Number of pages6
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume350
Issue number1333
DOIs
Publication statusPublished - 1 Jan 1995
Externally publishedYes

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