DNA abasic sites

Detection of DNA abasic site with light-up probes FISH to size the telomeric sequences... 

Greco NJ, Tor Y. Simple fluorescent pyrimidine analogue detect the presence of DNA abasic sites. J. Am. Chem. Soc. 2005 127 10784-10785. 

Vidal, A.E., Boiteux, S., Hickson, I.D., and Radicella, J.P. (2001) XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. EMBO J., 20, 6530-6539. 

Guillet, M., and Boiteux, S. (2002). Endogenous DNA abasic sites cause cell death in the absence of Apnl, Apn2 and Radi/Radio in Saccharomyces cerevisiae. EMBO/ 21, 2833-2841. 

An, N. White, H. S. Burrows, C. J. Modulation of the current signatures of DNA abasic site adducts in the alpha-hemolysin ion channel. Chem Commun 2012, 48, 11410-11412. 

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. " ... 

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... 

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. 

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-... 

E. coli Fpg protein (for- mamidopyrimidine-DNA glycosylase) Oxidized purines FAPY-A, FAPY-G, 8-oxo-G, 8-oxo-A, some abasic sites, to a lesser extent other modified purines... 

E. coli Nth protein (endonuclease III) Oxidized pyrimidines Ring-saturated or fragmented Thy residues, e.g. F Thy, Tg, 5-hydroxy-5-methylhydantoine, urea, DNA damaged at Gua, some abasic sites... 

Hogg, M., Wallace, S. S., and Doublie, S. (2004). Crystallographic snapshots of a replicative DNA polymerase encountering an abasic site. EMBOJ. 23, 1483-1493. 

Matsumoto, Y., and Bogenhagen, D. F. (1991). Repair of a synthetic abasic site involves concerted reactions of DNA synthesis followed by excision and ligation. Mol. Cell. Biol. 11, 4441-4447. 

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