N2- -dG lesion

All of these B[o]P-N2-dG adducts destabilize the DNA duplexes in a manner that depends on the adduct stereochemistry [53], Detailed thermodynamic studies of some of these adducts [103] and the effects of mismatched bases in the complementary strand opposite all four stereoisomeric B[a]P-N2-dG lesions (G ) in CG C and TG C sequence contexts have been published [104], The melting points of unmodified and B[o]P-modified duplexes are defined as Tm-the temperature at which 50% of the duplexes are dissociated into single strands and are in equilibrium with one another [105]. For convenience, we define the melting points of the modified duplexes by Tm (adduct) and the Tm of the unmodified duplexes by Tm (um). The difference in melting points ATm = Tm(adduct) - Tm (um) is -8 ((+)-trans-), -10 ((-)-trans-), -4 ((+)-ds-), and-5°C ((-)-as-anti-B[a]P-N2-dG) [53],... 

Figure 12.5 (a) Autoradiographs of dual excision products NER of (+)-cis-l, (+)-trans-l, and (-)-trans-/ 135mer duplexes in the 5 -.., CCATCG CTACC... sequence context (CC C-I in Figure 12.9) hybridized with a fully complementary strand with C opposite G. The duplexes were internally 32P 5 -end-labeled at the first C shown here at the sixth phosphodiester bond on the 5 -side of the B[o]P-N2-dG lesions (G ). The dual-incision products were obtained after incubation of the 135mer duplexes containing different stereoisomeric G lesions with nuclear extracts from human HeLa cells for 30 min at... 

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. 

Purified yeast Pol is able to perform limited nucleotide insertions opposite several DNA lesions such as TT (6-4) photoproduct, AAF-dG adduct, and (+) or ( )-trans-anti-BPDE-N2-dG adduct. Furthermore, Pol also catalyzes extension synthesis from opposite many types of lesions with varying efficiencies, including an AP site, cis-syn TT dimer, (64) photoproduct, AAF-dG adduct, (+) or (-)-trans-an//-BPDE-/V2-dG adduct, and an acrolein-derived dG adduct. Therefore, it has been proposed that Pol functions both as an insertion polymerase and an extension polymerase. It appears that the extension activity of Pol is versatile. Thus, it is believed that Pol is a major extension polymerase during translesion synthesis in eukaryotes. 

Zaliznyak, T., Bonala, R., Johnson, F., and de los Santos, C. (2006) Structure and stability of duplex DNA containing the 3-(deoxyguanosin-JV2-yl)-2-acetylaminofluorene (dG(N2)-AAF) lesion a bulky adduct that persists in cellular DNA. Chem. Res. Toxicol., 19, 745-752. 

These are all identical duplexes, except for the following differences the G6G7 and G6 G7 duplexes are identical in composition and 10S (+)-trans-onti-B[a]P-N2-dG adduct stereochemistry except that the lesions are positioned at either of the... 

In this connection, crystal structures of the (+) - trans-anti-1 i a P D E- N2-dG adduct in the Y-family lesion bypass DNA polymerase IV (Dpo4) (see also Chapter 15 by Chandani and Loechler) from the archaeon Sulfolobus solfataricus reveal that the favored P domain is preserved in the enzyme in this case [51], Overall, a survey of crystal structures of DNA damaged by polycyclic carcinogenic chemicals shows that structures observed in DNA duplexes in solution by high-resolution NMR methods are often observed in polymerases [37] however, the preferred P domain can be overridden by strong lesion-polymerase interactions, as was manifested in a crystal structure of a B[a]PDE-derived adenine lesion [52],... 

Rechkoblit, O.. Zhang, Y., Guo, D., Wang, Z Amin, S., Krzeminsky, J., Louneva, N., and Geadntov, N.E. (2002) trans-Lesion synthesis past bulky benzo[o]pyrene diol epoxide N2-dG and f/ -dA lesions catalyzed by DNA bypass polymerases. J. Biol. Chem.,... 

More is known about translesion synthesis of the major adduct of AAF and N2-dG adducts in E. coli than any other adducts/lesions, as outlined in this section. 

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