R. Rimini et al., INTERACTION OF NORMAL AND MUTANT SRY PROTEINS WITH DNA, Philosophical transactions-Royal Society of London. Biological sciences, 350(1333), 1995, pp. 215-220
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 biochemic
al properties of mutant SRY proteins from five patients with complete
gonadal dysgenesis: two bind and bend DNA almost normally, two bind in
efficiently but bend DNA normally, and one binds DNA with almost norma
l affinity but produces a different angle. The mutations with moderate
effect on complex formation can be transmitted to progeny, the ones w
ith severe effects on either binding or bending are de nova. 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 essenti
al for the expression of genes involved in testis differentiation.