Synopsis
DNA cross-linking is seen with many bifunctional electrophiles, i.e., compounds with two separate electrophilic centers. Depending upon the geometry of the atoms in the DNA bases that react, intra- and interstrand DNA cross-links result. These are generally very detrimental to the progress of DNA polymerases. Thus, some of these compounds are used to treat cancers, in that they have the effect of slowing the growth of rapidly dividing tumor cells, in which DNA synthesis is robust. However, DNA cross-linking can also cause miscoding and mutations. Another phenomenon is DNA-protein cross-linking, which has been observed but is not well understood. Enzymes are present in cells to repair DNA cross-links. However, these repair systems can negate the effects of drugs used to treat tumors, and some therapy regimens include blocking the repair.
Introduction
Cross-linking is one of the most disruptive events that can occur with DNA, particularly interstrand cross-linking and...
References
Barker S, Weinfeld M, Murray D (2005) DNA-protein crosslinks: their induction, repair, and biological consequences. Mutat Res 589:111–135
Friedberg EC, Walker GC, Siede W et al (2006) DNA repair and mutagenesis. ASM Press, Washington, DC
Kalapila AG, Loktionova NA, Pegg AE (2009) Effect of O 6-alkylguanine-DNA alkyltransferase on genotoxicity of epihalohydrins. Environ Mol Mutagen 50:502–514
Liu L, Williams KM, Guengerich FP et al (2004) O 6-Alkylguanine-DNA alkyltransferase has opposing effects in modulating the genotoxicity of dibromomethane and bromomethyl acetate. Chem Res Toxicol 17:742–752
Loecken EM, Guengerich FP (2008) Reactions of glyceraldehyde 3-phosphate dehydrogenase sulfhydryl groups with bis-electrophiles produce DNA-protein cross-links but not mutations. Chem Res Toxicol 21:453–458
Loecken EM, Dasari S, Hill S et al (2009) The bis-electrophile diepoxybutane cross-links DNA to human histones but does not result in enhanced mutagenesis in recombinant systems. Chem Res Toxicol 22:1069–1076
Minko IG, Kozekov ID, Kozekova A et al (2008) Mutagenic potential of DNA-peptide crosslinks mediated by acrolein-derived DNA adducts. Mutat Res 637:161–172
Peterson LA, Harris TM, Guengerich FP (1988) Evidence for an episulfonium ion intermediate in the formation of S-[2-(N 7-guanyl)ethyl]glutathione in DNA. J Am Chem Soc 110:3284–3291
Stone MP, Huang H, Cho Y-J et al (2010) Interstrand DNA cross-linking 1, N 2-Deoxyguanosine adducts from α, β-unsaturated aldehydes: structure-function relationships. In: Broyde S, Geacintov NE (eds) The chemical biology of DNA damage. Wiley-VCH Verlag, Weinheim, pp 203–216
Straub K, Kanne D, Hearst JE et al (1981) Isolation and characterization of pyrimidine-psoralen photoadducts from DNA. J Am Chem Soc 103:2347–2355
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Guengerich, F.P. (2014). DNA Cross-linking. In: Bell, E. (eds) Molecular Life Sciences. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6436-5_621-1
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DOI: https://doi.org/10.1007/978-1-4614-6436-5_621-1
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Publisher Name: Springer, New York, NY
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