Base sequence context

The population balance between these differing conformations is governed by the specific nature of the aromatic carcinogen as well as the neighboring base sequence contexts. A predominant (90-95%) B-conformer has been experimen-... 

Extensive studies by NMR methods have shown that the conformations of PAH diol epoxide-N2-dG and - N6-dA adducts in double-stranded DNA depend markedly on the stereochemistry, PAH topology, and base sequence context Earlier work has been summarized by us [53]. Since then, we have published the NMR solution structures of a number of other DNA adducts [79, 88, 89, 92]. The structural properties of various DNA adducts have been reviewed more recently by Lukin and de los Santos [93]. The basic structural motifs, based on our work and that of others [94—98] that are relevant to the NER studies described in this chapter, are summarized in Figure 12.3. Computational analyses have provided insights into the origins and stereochemistry dependence of these remarkably different adduct conformations [26, 42, 47, 54, 99]. In the following, we summarize the main features of these different conformations. 

Dependence of NER of the 10S [+)-trans-a nti-B[a]P- N2-dC Adduct on Base Sequence Context... 

The structural properties of B[a]P diol epoxide-derived DNA adducts depend not only on their stereochemical properties as described above, but also on the local base sequence contexts. In order to gain some insights into these phenomena, we focused on the major, biologically significant 10S (+)-tram-anti-B[a]P-N2-dG adduct in the sequence contexts shown in Figure 12.9. We first discuss what is special... 

Figure 12.9 (a) Base sequence contexts investigated, where C represents the 10S (+)-trar)S-or)t/-B[o]P-/ /2-dC adduct in all sequences. The duplex I6C7 is identical to C6C7 except for the designated 2 -deoxyinosine (I). (b) Structures for guanine... 

Dependence ofNER of the 70S (+)-trans-anti-B[aJP-N2-dG Adduct on Base Sequence Context 283... 

Yan, S., Wu, M., Buterin, T., Naegeli, H., Geadntov, N.E., and Broyde, S. (2003) Role of base sequence context in conformational equilibria and nucleotide excision repair of benzoja] pyrene diol epoxide-adenine adducts. Biochemistry, 42, 2339-2354. 

Rodriguez, F.A. (2007) Nudear magnetic resonance solution structure of covalent polycydic aromatic cardnogen-DNA adducts influence of base sequence context and carcinogen topology. PhD Thesis. New York University, New York. 

Amin, S and Geadntov, N.E. (2003) Effects of base sequence context on translesion synthesis past a bulky (+)-trans-anti-B[a]P-N2-dG lesion catalyzed by the Y-family polymerase pol k. Biochemistry, 42, 2456-2466. 

Zhang, X., and Mathews, C. K. (1995). Natural DNA precursor pool asymmetry and base sequence context as determinants of replication fidelity. J. BioL Chem. 270, 8401-8404. 

R306 Y. Cai, D. J. Patel, S. Broyde and N. E. Geacintov, Base Sequence Context Effects on Nucleotide Excision Repair , J. Nucleic Acids, [online computer file], 2010 no pp.. Avail. URL http //downloads.sage-hindavi.com/joumals/ jna/2010/174552.pdf. 

In contrast to the overwhelming affect of conversion of an A/T base pair in AQ-DNA(4) to a T/A base pair in AQ-DNA(5) on radical cation transport, the identical change in AQ-DNA(6) and AQ-DNA(7) has no measurable effect on the amount of strand cleavage observed at GG7 or GG2i [27]. It is apparent from consideration of these results that the effect of a change in base sequence must be considered in the context of the surrounding base pairs and not in isolation. 

Incorporation of selenocysteyl-tRNASer into protein in response to the UGA codon requires SELB (the protein product of the selB gene in E. coli). SELB is homologous in sequence to EF-Tu and probably replaces it in translation by specifically recognizing selenocysteyl-tRNA and UGA in the appropriate sequence context. Selenocysteyl-tRNASer, in combination with SELB, must be capable of competing with termination factors for the translation of the termination codon when it occurs in the right context of bases. This process is known as site-specific variation in translation elongation. 

Contrary to H-bonded nucleic acid base pairs discussed in the previous section, the nature of intermolecular interactions in complexes of stacked bases was analyzed more extensively. The values of minimal, maximal, and average total stabilization energies, corrected for BSSE, for a set comprising over 80 stacked bases, are plotted in Fig. 20.1. In the case of guanine-adenine and adenine-cytosine complexes, the results are presented for two sequence contexts, i.e., A/G-G/A and A/C-C/A. The symbol AA denotes the 2-oxo-adenine - complexes of oxidized bases, and this... 

Hansen, J. E., Lund, O., Tolstrup, N., Gooley, A. A., Williams, K. L. Brunak, S. (1998). NetOglyc prediction of mucin type O-glycosylation sites based on sequence context and surface accessibility. Glycoconj J15,115-30. 

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