DNA structure: Revisiting the Watson–Crick double helix
Institute of Bioinformatics and Applied Biotechnology, ITPL, Bangalore 560 066, India and Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India
Watson and Crick’s postulation in 1953, exactly 50 years ago, of a double helical structure for DNA, heralded a revolution in ourunderstanding of biology at the molecular level. The fact that it immediately suggested a possible copying mechanism for the genetic material aroused the maximum interest, but the structure itself (often referred to as the B-DNA structure, by association with the corresponding X-ray fibre pattern) has also attained an almost iconic status. It was for a long time regarded as being the only biologicallyrelevant structure, even though Watson and Crick had themselves pointed out that the structure could readily undergo changes, depending on the environment. Subsequent studies on synthetic poly-nucleotides as well as naturally occurring DNA sequences with certain repeat patterns, have established that the DNA molecule could have intrinsic, as well as environment-induced, structural polymorphism.Some of the structures show only minor differences, from the canonical structure, while a few are completely different, even in their essential features, such as handedness, base-pairing scheme or number of strands. The various DNA structures have THE right-handed double helical structure (Figure 1) proposed in 1953 by Watson–Crick for deoxyribose nucleic acid (commonly known as DNA) is the mostwellrecognized structure for this polymeric molecule1. While Watson–Crick were undoubtedly the first to propose an essentially correct model for DNA structure, a wide variety of available data was used by them to arrive at this ‘canonical’ model for DNA, in particular the nucleotide base composition data of Chargaff (Table 1) and information from the X-ray fibre diffraction pattern (Figure 2) ofB-form DNA, as recorded by Rosalind Franklin2. It was commonly believed for several decades, that this B-form is the only structure of DNA that has biological relevance, even though Rosalind Franklin’s fibre diffraction data2,3 for A and B forms (Figure 2) had clearly shown that the DNA molecule could readily undergo structural transitions depending on the environment, viz. variation in relativehumidity in this case. Fibre diffraction studies in the sixties and seventies also revealed several other forms of DNA structure for synthetic oligo- and polynucleotides, depending on the base sequence and environment. Subsequent biochemical and structural studies showed that regions of genomic DNA, under various
been characterized as A, B, C, etc. and there is a DNA structure associated with 18other letters of the English alphabet. Only the letters F, Q, U, V and Y are left to choose from, to describe any new forms of DNA structure that may appear in future! Apart from these structures, with a one-letter ‘name’, there are several other generic descriptions of DNA structure and many such structures have been characterized in recent years. It is reasonable to expect that the 3 billion basepairs in the human genome (leading to a 2 m long molecule which is packaged in a microscopic size nucleus) will exhibit a variety of polymorphic forms, which could be important for the biological packaging as well as function of DNA. It is also clear that the ideal and canonical Watson–Crick DNA structure is indeed just that – an ideal and aesthetic representation of the DNA molecule, whichactually possesses a chameleonlike property of adapting itself to its environment and function by twisting, turning and stretching. Some of these structures are discussed here as also the lacunae in our current understanding of the dynamics of DNA structure. physiological conditions, can assume different structures, particularly when some well-defined sequence motifs or repeats occur. It was probably...