A MOLECULAR MECHANISM FOR COMBINATORIAL CONTROL IN YEAST - MCM1 PROTEIN SETS THE SPACING AND ORIENTATION OF THE HOMEODOMAINS OF AN ALPHA-2 DIMER

DNA recognition sequences for dimeric proteins typically contain two types of information. The first is the DNA sequence of each half-site, and the second is the arrangement of these half-sites. We show that dimers of the yeast homeodomain protein alpha-2, although able to read the first type of information, lack the ability to assess the second type. Rather, alpha-2 dimers bind with equal affinity to artificial operators in which the two half-sites are arrayed as inverted repeats, as direct repeats, or as everted (inside-out) repeats. We show that a second protein - MCM1 - sets the exact spacing and orientation of the homeodomains in the alpha-2 dimer so that they accommodate only the geometry of the naturally occurring operators. These experiments show directly how the target specificity of a homeodomain protein is raised by an auxiliary protein, allowing it to distinguish the biologically correct operators from closely related sequences in the cell.