Sequence-dependent variations, local

Explain why local DNA structure depends on base sequence and appreciate how proteins that bind DNA in a sequence-dependent manner exploit this sequence-dependent variation. 

Computer molecular modeling of duplex DNA will play an important role in sorting out the relative role of crystal paclang forces and intrinsic sequence-dependent variations in local helical structure (28) and in exploring the deformability of DNA and its sequence dependence. 

When the first crystal structure for the B-DNA was reported [53], it was observed that the relative orientation of two basepairs was non planar and there existed a sequence dependent variation in this local structural... 

DNase I is an endonuclease that catalyzes the hydrolysis of phosphodiester bonds by nucleophilic attack on 3 O-P. The enzyme activity requires divalent metal ion cofactors such as Mg " and Ca or Mn +. DNase I binds to the minor groove of dsDNA and cleaves each strand independently. The often observed sequence preference and different cleavage rates of DNase I are largely structural and are related to sequence-dependent variations of the double helix such as groove width, local rigidity to bending, radial asymmetry, and accessibility to backbone phosphates (26,29,33,34). 

The structural variations can affect the width of the major groove, the extent of base stacking, as well as the tilt of the basepairs to each other. The local conformational changes are sequence dependent and can be intrinsic properties and thus permanent occurrences they can, however, also be induced by protein binding. The DNA sequence can thus serve a double purpose for the recognition between DNA and protein. 

Probes have now been described that are tailored in their shapes to corresponding sequence-dependent shapes along the DNA helix. These probes can therefore be used to examine the topology of the DNA helix, or, in other words, the local variations in structure that occur along the strand as a function of sequence and as a function of biological location. After all, the DNA sequence encodes both the amino acids needed for the construction of protein and also the recognition sites for the binding of... 

The same oligosaccharides may play different roles, depending on their localization in an organism. Conversely, important variations from species to species may be observed in sequences with similar functions. At first sight the detailed structure of these chains should not be very important, but we really do not know. 

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