Sugar lesions

Similar experiments have been carried out with dGuo (Gromova et al. 1998). The free base, 2-dRL sugar lesions of analogous to those reported above (now... 

One of the most important sugar lesion is the 3 -phosphoglycolate that is typically formed in the presence of O2 (for its excision by purified HeLa cell extracts see Winters et al. 1992). Specifically deuterated nucleoside triphosphates were used for incorporation into dsDNA by PCR (Balasubramanian et al. 1998). Hydroxyl radicals were generated by a Fenton reaction, and the yields of free 3 -phosphate end groups, 3 -phosphoglycolate and 5 -aldehyde were measured. Depending on the position of the deuteration, the yields vary with respect to a non-deuterated sample (Table 12.9). 

The sugar lesions FUR and 5-MF (Joshi and Ganesh 1994), as well as DNA-ad-ducts (Park et al. 1989) have also be detected with the help of HPLC. 

The interaction of the anti-tumour antibiotic bleomycin with DNA under conditions of limiting oxygen results in the production of a free nucleic base and an oxidatively damaged sugar-lesion. Studies on d(CGCTGCGT) demonstrate... 

As discussed earlier, guanine (G), adenine (A), cytosine (C), and thymine (T) in DNA can be modified by in vivo reactive species or different exogenous factors giving rise to a plethora of DNA base lesions. In vitro stndies with DNA or model componnds have shown that almost seventy different types of base lesions can be prodnced in DNA [55]. However, qnantification of all these lesions in cellular DNA is difficult. As a result, only abont 20 different base and sugar lesions have been identified so far in cells [56]. These include both simple and complex base lesions. Simple base lesions mainly consist of different oxidatively damaged products of DNA bases whereas complex base lesions mainly include bulky lesions like DNA-DNA and DNA-protein crosslinks. It should be noted that as the oxidation potential of G is the lowest among all the bases [57, 58], it is more freqnently attacked by different reactive species than others. Therefore, we will here mainly consider the formation of different simple base lesions related to the modifications of guanine in DNA by different in vivo reactive species. 

ROS and RON can react with the DNA molecule and induce purine or p)u imidine base or sugar lesions, nitration and deaminations of purines, and DNA-DNA or DNA-protein cross-links (Dizdaroglu et al., 2002). These processes lead to mutations and impaired transcriptional and posttranscriptional processes and compromise protein synthesis (Colurso et al., 2003). In addition, DNA damage, oxidative phosphorylation, and altered cell metabolism may lead to apoptosis and promote neuronal death (Fishel et al., 2007 Becker and Bonni, 2004). ROS and RNS can also attack amino acids, leading to the formation of carbonyl derivatives (Stadtman and Levine, 2003). Oxidation of protein also leads to protein fragmentation and protein cross-linking. In addition, peroxynitrite and a hydroxyl radical can react with tyrosine and form other indexes of protein oxidation,... 

In some circumstances, DNA radical lesions can react with an adjacent base or the sugar residues. In these cases, a single radical hit can be transformed into two adjacent damage sites on the DNA. The resulting tandem lesions may present special challenges to DNA replication and repair systems. ... 

Under low oxygen conditions, C5 -sugar radicals can react with the base residue on the same nucleotide. In purine nucleotides, the carbon-centered radical 91 can add to the C8-position of the nucleobase (Scheme 8.31). Oxidation of the intermediate nucleobase radical 92 yields the 8,5 -cyclo-2 -deoxypurine lesion 93197,224,225,230-233 Similarly, in pyrimidine nucleotides, the C5 -radical can add to the C6-position of nucleobase. Reduction of the resulting radical intermediate yields the 5, 6-cyclo-5,6-dihydro-2 -deoxypyrimidine lesion 94,234-236... 

Perhaps the best-characterized lesion in DNA associated with uv inactivation and mutagenesis is that involving the intrastrand photodimerization of adjacent thymine residues this lesion is almost wholly repaired by photodissociation of the dimers at shorter wavelengths in the photoreactivation process. Production of the chh dimer in this case, promoted by the configuration of adjacent molecules on the same sugar-phosphate strand, must however involve a rotational displacement of 36°, following the reduction of 0.6 A in molecular separation. 

Scheme 2.2 Examples of reactions catalyzed by and RNA by the protein AlkB [54] (R = sugar al

As can be seen from this table, the detectable products amount to 35% of OH at most. Moreover, dsDNA gave rise to markedly lower yields than ssDNA. Whether this is due to incomplete OH scavenging in these systems due to low-molecular-weight impurities is as yet unknown. Obviously, as we know from other studies, there are more products formed such as Iz, Z, cA, cG, 5HmU, 5ForU, Fo and hydantoin lesions (see below) than have been determined in this study. Moreover, there is an attack of OH at the sugar moiety that is generally believed not to exceed 20% by much (see, however, Sect. 12.4.4). Thus, there is a gap in the material balance. The material balance is especially poor in the absence of 02. 

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