Abasic sites

The abasic sites (3, Scheme 8.2) resulting from the loss of alkylated bases from DNA are both cytotoxic and mutagenic. " The cyclic acetal (3) exists in equilibrium with small amounts (—1%) of the open chain aldehyde (4). The acidic nature of a-proton in the aldehyde form of the abasic lesion facilitates 3-elimination of the 3 -phosphate residue to yield a strand break. " This reaction occurs with a half-life of about 200 h under physiological conditions (pH 7.4, 37°C), but can be accelerated by heat, basic conditions, or the presence of various amines. " ... 

The /3-value in this area is 0.6 0.1 A"1 for our injection system. A / -value in this order seems to be typical, as the articles by F.D. Lewis and V. Shafirovich in this volume show. Also, the data of Fig. 5 are interesting. They demonstrate that distance holders in the bridge whose ionization energies are too high to become oxidized by 7 only slightly influence the rate of the electron injection in our system [7]. However, an abasic site (H) increases... 

In the perfectly paired double strand 22, the yield of product PGgg> which indicates the amount of charge that has reached the hole trap GGG, is 68%. But if the intermediate G C base pair is exchanged by a G T mismatch, the efficiency of the charge transport drops to 23%. With an abasic site (H) opposite to G the hole transport nearly stops at this mismatched site (Fig. 15). We have explained this influence of a mismatch on the efficiency of the charge transport by a proton transfer from the guanine radical cation (G2 +)... 

Fig. 15 Influence of mismatches on the efficiency of hole transfer through double strands 23 and 24 where the cytidine (C) is exchanged by thymidine (T) and an abasic site (H), respectively. In 25 guanosine is exchanged by N-methylguanosine (see Scheme 6), and C by an abasic site (H)...

Besides the direct oxidation products of base residues of DNA, such as the oxidation of thymine (43) and guanine (160) residues meutioued in Sections IV.B.2 and IV.B.3, ROS and other factors may bring about detachmeut of base residues from the DNA strand, leading to formation of aldehyde abasic sites on the main chain, as shown in... 

Table 1. Oligonucleotide sequences. - coumarin, - abasic site.

Figure 2a compares the time-resolved Stokes shift of the normal sequence and the abasic sequence. For ease of comparison, the data is shifted to overlap the sequences at early times. In the first nanosecond, the Stokes shifts from both sequences overlap almost perfectly. This results suggests that there is not a large scale collapse of the normal DNA structure at the abasic site. However after 1 ns, the abasic sequence has additional dynamics beyond those of the normal sequence. The fit of the abasic sequence has the same logarithmic component of the normal sequence fit, but with an additional exponential term for the fast rise in the Stokes shift after 1 ns S(t) = S0 + A0 logl0(t/t0) + 4,(l-exp(-f/r)), with an exponential time constant r of 25 ns. 

An interesting candidate for this motion is suggested by the molecular dynamics simulations of Barsky et al [11]. On a nanosecond time scale, they see a flipping of the abasic sugar from an intrahelical to an extrahelical position. This flip is correlated with a filling of the abasic site with water. Because our probe is sensitive to local polarity, it should be quite sensitive to this process. 

As the word suggests, an abasic site (apurinic/apyrimidinic site, AP) lacks the base, but the DNA backbone is more or less intact. The simplest AP is a 2-dR site, formed... 

Chaudry MA, Weinfeld M (1997) Reactivity of human apurinic/apyrimidinic endonuclease and Escherichia coli exonulcease III with bistranded abasic sites in DNA. J Biol Chem 272 15650-15655 Chaudry MA, Dedon PC, Wilson DM III, Demple B, Weinfeld M (1999) Removal by human apurinic/ apyrimidinic endonuclease 1 (Ape 1) and Escherichia coli exonuclease III of 3 -phosphoglyco-... 

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