DNA BENDING BY THE A1 AND ALPHA-2 HOMEODOMAIN PROTEINS FROM YEAST

Structural and biochemical studies of monomer homeodomain-DNA complexes have not so far revealed any cases of pronounced DNA distortion. In this paper we show that multimeric complexes of the yeast homeodomain proteins a1 and alpha 2 induce significant bends in their operators upon binding. Based on a series of circular permutation experiments, we found that a dimer of alpha 2 bound to operator DNA produced a mild bend in the DNA, whereas the alpha 2-MCM1-DNA and the a1-alpha 2-DNA complexes exhibited much sharper bends. As these latter two complexes represent the in vivo form of DNA-bound al and alpha 2, we conclude that, in the cell, these homeodomain proteins are associated with pronounced bends in DNA. We discuss possible roles for these bends in transcriptional repression.