DNA INVERTED REPEATS AND HUMAN DISEASE

John J. Bissler

The Children's Hospital Research Foundation, Cincinnati, Ohio

4. CRUCIFORM FORMATION

Energetically, it may seem very unlikely that a stem loop structure with less base pairing in the unpaired loop, would form in any abundance in DNA because the entire duplex structure would be favored on the basis of overall basepairing. Isolated linear DNA has a formidable energy barrier shielding the encoded information. The barrier consists of the energy of the hydrogen bonding and stacking forces that hold complementary strands of DNA together. The energy added to the molecule in living cells to make this information more readily available for transcription and replication is the unwinding of the DNA (9). The unwinding of DNA consists of twisting the two strands in the opposite direction of the helical coil. This energy strains the hydrogen bonds and stacking forces. The strain is relieved by the writhe of the DNA duplex upon itself, similar to twisting of a phone cord after it has been stretched. The relationship between twist and writhe is a constant known as the linking number. The negative superhelical tension can be restrained by wrapping DNA around proteins such as histones. The negative superhelical tension is dynamic, and is affected by both transcription and replication, as well as by changes in protein-DNA binding such as mediated histone acetylation (10,11). This superhelical tension is the driving energy for the formation of alternative DNA structures (12).