Role of DNA Sequence

Baird, P.B. Dervan, and D C. Rees. Structural effects of DNA sequence on T-A recognition by hydroxypyrrole/pyr-role pairs in the minor groove. J. Mol. Biol. 2000, 295, 557-567. 

The dimer of the hormone-receptor complex should scrutinize an infinity of sequences before finding its FIRE. The role of the hormone in the recognition of the HRE seems to be that of dramatically increasing the velocity of DNA sequence recognition, that is to say, it binds and disconnects more quickly to sequences of nonspecific DNA. When it finds the sequence of its HRE, a bond of affinity is formed that is similar to that of hormone-receptor interaction (Kd in the nM range). 

Portugal J, Waring MJ (1987) Interaction of nucleosome core particles with distamycin and echinomycin analysis of the effect of DNA sequences. Nucleic Acids Res 15(3) 885-903 Povirk LF, Goldberg IH (1987) A role of oxidative DNA sugar damage in mutagenesis by neocarzino-statin and bleomycin. Biochimie 69(8) 815-823... 

The centromere (Fig. 24-9) is a sequence of DNA that functions during cell division as an attachment point for proteins that link the chromosome to the mitotic spindle. This attachment is essential for the equal and orderly distribution of chromosome sets to daughter cells. The centromeres of Saccharomyces cere-visiae have been isolated and studied. The sequences essential to centromere function are about 130 bp long and are very rich in A=T pairs. The centromeric sequences of higher eukaryotes are much longer and, unlike those of yeast, generally contain simple-sequence DNA, which consists of thousands of tandem copies of one or a few short sequences of 5 to 10 bp, in the same orientation. The precise role of simple-sequence DNA in centromere function is not yet understood. 

The Genome Sequencing Center focuses on the large-scale generation and analysis of DNA sequences. They have played an important role in the Human Genome Project. They also sequenced the genome of other species such as the chicken, C. elegans, planarian, chimpanzee, and drosophila. 

Cloning techniques have also played an important role in the development of DNA sequencing. Cloning allows many copies of the DNA to be made so that enough material to sequence is available. 

The structure proposed by Watson and Crick has two properties of central importance to the role of DNA as the hereditary material. First, the structure is compatible with any sequence of bases. The base pairs have essentially the same shape (see Figure 1.6) and thus fit equally well into the center of the double-helical structure of any sequence. Without any constraints, the sequence of bases along a DNA strand can act as an efficient means of storing information. Indeed, the sequence of bases along DNA strands is how genetic information is stored. The DNA sequence determines the sequences of the ribonucleic acid (RNA) and protein molecules that carry out most of the activities within cells. 

Secondary structures are currently the most useful structural elements with respect to computer analysis. Secondary structrures are mostly known for RNAs and proteins but they also play important roles in DNA. Potential secondary structures can be easily determined and even scored via the negative enthalpy that should be associated with the actual formation of the hairpin (single strand) or cruciform (double strand) structure. Secondary structures are also not necessarily conserved in primary nucleotide sequence but are subject to strong positional correlation within the structure. Three-dimensional aspects of DNA sequences are without any doubt very important for the functionality of such regions. However, existing attempts to calculate such structures in reasonable time met with mixed success and cannot be used for a routine sequence analysis at present. 

Other oncogenes were soon discovered in a variety of animal viruses, and as the techniques of DNA sequencing became more routine, a surprising number of these oncogenes were matched up with normal genes in animals and even in humans. But what was the role of these proto-oncogenes Most of them have now been shown to code for enzymes that help control the growth and differentiation of cells. In many instances, the enzymes are kinases that phosphorylate serine, threonine or tyrosine residues of other... 

There is also a need for further base-line studies to support this physiological work. Although there are now some algorithms to identify PQS, none of these are very well developed, and further work is required to refine them. It would be valuable to have a model that could predict both the structure (especially antiparallel V5. parallel folds) and the thermodynamic stability of sequences, in the manner currently possible for duplex DNA. This goal will require more detailed analysis of the role of the sequences, and hence a significant extension of the analysis to date. Another issue is that, to date, almost every biophysical study has looked at G-quadruplex formation from a single strand of DNA. There is a need to better understand the equilibrium between quadruplex and duplex structures in a more native context. 

---