Scheme of the putative mechanistic roles of cruciform binding proteins in transcription, DNA replication, and DNA repair. A) A model for the structure-specific binding of transcription factors to a cognate palindrome-type cruciform implicated in transcription. The equilibrium between classic B-DNA and the higher order cruciform favors duplex DNA, but, when cruciform binding proteins are present, they either preferentially bind to and stabilize the cruciform or bind to the classic form and convert it to the cruciform. This interaction results in both an initial melting of the DNA region covered by transcription factor and an extension of the melt region in both directions. The melting region continues to extend in response to the needs of the active transcription machinery. B) A model for the initiation of replication enhanced by extrusion to a cruciform structure. Dimeric cruciform binding proteins interact with and stabilize the cruciform structure. The replisome is assembled concomitantly and is assumed to include polymerases, single-strand binding proteins and helicases. C) Model for the influence of cruciform binding proteins on DNA structure in DNA damage regulation. Naked cruciforms are sensitive to DNA damage and are covered by proteins in order to protect these sequences from being cleaved. In these cases, a deficiency in cruciform binding proteins can lead to DNA breaks. Here, cruciform-DNA complexes can also serve as scaffolds to recruit the DNA damage machinery.