Intrinsically bent DNA.

Abstract

Intrinsically bent or curved DNA molecules result when special base sequences or structural motifs are repeated in phase with the DNA helical repeat (~10.5 bp’/turn). This places the recurrent elements along the same side of the double helix so that small bends associated with them add constructively to generate a large global curvature. Many base sequences can impart systematic curvature to DNA, but most such bends are small compared with the special effect produced by runs of homopolymeric dA.dT base pairs (“Atracts”), each tract about half a helical turn long and repeated at lo-11-bp intervals. Bent DNA was discovered by the laboratories of Englund and Crothers (1) during study of a minicircle DNA from the kinetoplast body of Leishmania tarentolae, in which appropriately phased A-tracts occur prominently (1, 2). The anomalous gel mobilities shown by bent DNA molecules have provided crucial experimental insight into the origin and nature of DNA bending. Application of early theories describing gel mobilities for molecules undergoing reptational migration (3,4) leads one to expect slower motion for bent molecules because they have a shortened end-to-end distance. This criterion has proved to be a reliable guide to experimental properties, even though it ignores significant theoretical issues 6). A critical experiment for diagnosing the presence and location of DNA bends has been comparison of the electrophoretie properties of circularly permuted DNA molecules, all of the same length but each having the bend at a different position. In the first application of this concept, Wu and Crothers (6) were able to identify a locus containing phased dA.dT tracts which provided the primary source of bending in Leishmaniu kinetoplast minicircle DNA. Since that time, phased dA.dT tracts have been identified in various gene regulatory regions (7-lo), but the biological function of intrinsically bent DNA remains uncertain.