Stable internal loops in DNA:
How far can DNA adopt unusual structures?

Shan-Ho Chou* & Ko-Hsin Chin

Institute of Biochemistry

National Chung-Hsing University, Taichung, 40227, Taiwan


The study of unusual nucleic acid folds has launched into a new dimension recently, due to the unexpected finding of novel biological functions exhibited by these molecules. One of the most common motifs is the symmetric internal loop, which can results with either a double helical structure with consecutive non-canonical base pairs yet extensive base stacking, or a distorted double helix suitable for interacting with other molecules. While internal loops are widespread in RNA and have been subject to extensive studies, internal loops in DNA are less well characterized and are generally believed to be less stable. Although consecutive mismatches in DNA are statistically unlikely to arise from replication errors, they may occur in the fold-back structures of the purine-rich strand of highly repetitive sequences, which are prevalent in functionally important regions of eucaryotic centromeres and telomeres. The purine-rich strand may form fold-back structures when it is separated from the pyrimidine-rich strand in vivo through the preferential protein binding of the pyrimidine-rich strand or under physiological stress. Such fold-backs usually exhibit high melting temperatures even with various kinds of internal loops. Further investigation of DNA internal loops in such sequences is essential toward understanding their possible biological functions. In this respect, we now report the stable formation of two distinct types of internal loop structures in DNA, i.e. a distorted double helix and a zipper-like intercalation motif. A series of DNA internal loops, including 2 x 2, 2 x 3, 3 x 3, and 4 x 4 internal loops of these two types will be discussed. The unexpected finding of these stable motifs greatly increases the limited repertoire for DNA irregular folds.