DNA backbone

These results indicate that the repressor fragment is unable to impose upon the nonconsensus sequence on the right-hand side of OR3 the DNA conformation that is required for tight binding between repressor and DNA. It thus appears that the weaker binding of repressor to OR3 is a consequence of the resulting less perfect "fit" between protein and DNA backbone (see Figure 8.13). 

Residues 3, 5, 6, and 8 in the N-terminal arm lie in the minor groove and form contacts with either the edge of the bases or with the DNA backbone. Almost all homeodomains contain four conserved residues, Asn 51, Arg 53, Trp 48 and Phe 49, in the middle of the long recognition helix. The first two conserved polar residues interact with DNA. The second two are part of the hydrophobic core of the homeodomain, and are important for the accurate positioning of the recognition helix and the N-terminal arm with respect to... 

Figure 9.11 Amino acid sequences of homeodomains from four differenf franscription factors Anfp is from fhe Antennapedia gene in the fruitfly Drosophila, a2 is from the yeast Mat o2 gene, eng is from fhe engrailed gene in Drosophila and POU is from fhe POU homeodomain in the mammalian gene Oct-1. Residues colored green form the hydrophobic core of the homeodomain, blue form nonspecific interactions with the DNA backbone and red form contacts with the edges of the DNA bases.

Both domains of the POU region bind to DNA by the usual combination of non specific binding to the DNA backbone and specific binding to the bases. The contacts between the homeodomain and DNA are similar to those of the engrailed homeodomain (compare Figures 9.10b and 9.15a) and the... 

Protein-DNA backbone interactions determine DNA conformation Conformational changes of DNA are... 

A second explanation of the ability of oxidative stress to cause DNA damage is that the stress tri ers a series of metabolic events within the cell that lead to activation of nuclease enzymes, which cleave the DNA backbone. Oxidative stress causes rises in intracellular free Ca, which can fiagment DNA by activating Ca -dependent endonucleases (Orrenius etal., 1989 Farber, 1990 Ueda and Shah, 1992) in a mechanism with some of the features of apoptosis (see Wyllie, 1980). An example of apoptosis is the killing of immature thymocytes by glucocorticoid hormones, which activate a cell-destructive process that apparently involves DNA fragmentation by a Ca -dependent nuclease. 

Many compounds that damage DNA via radical intermediates have been identified. Some of the agents, such as bleomycin and the enediynes, damage DNA primarily through abstraction of hydrogen atoms. ° In these cases, chemical reactions are directed to certain positions on the DNA backbone by noncovalent binding that places the reactive intermediates in close proximity to particular deoxyribose sugar residues. Similar to the reactions of HO described above, small radicals, such as... 

Fig. 13 Results from the quantum calculations on the duplex sequence 5 -GAGG-3. In a, the sodium ions and their solvating water molecules are located at positions near the phosphate anions of the DNA backbone. In b, one sodium ion is moved from near a phosphate anion to N-7 of a guanine, which molecular dynamics calculations show to be a preferred site. The balloons represent the hole density on the GAGG sequences with the two different sodium ion orientations. The radical cation clearly changes its average location with movement of the sodium ion...

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