Multiply damaged sites

Linear energy transfer Locally multiply damaged sites Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry... 

Campbell JM, Schulte-Frohlinde D, von Sonntag C (1974) Quantum yields in the UV photolysis of 5-bromo-uracil in the presence of hydrogen donors. Photochem Photobiol 20 465-467 Chapman JD (1984) The cellular basis of radiotherapeutic response. Radiat Phys Chem 24 283-291 Chatterjee M, Mah SC, Tullius TD, Townsend CA (1995) Role of the aryl iodide in the sequence-selective cleavage of DNA by calicheamicin. Importance of thermodynamic binding vs kinetic activation process. J Am Chem Soc 117 8074-8082 Chaudry MA, Weinfeld M (1995) The action of Escherichia coli endonuclease III on multiply damaged sites in DNA. J Mol Biol 249 914-922... 

Ward JF, Blakely WF, Joner El (1985) Mammalian cells are not killed by DNA single-strand breaks caused by hydroxyl radicals from hydrogen peroxide. Radiat Res 103 383-392 Ward JF, Webb CF, Limoli CL, Milligan JR (1990) DNA lesions produced by ionizing radiation Locally multiply damaged sites. In Wallace SS, Painter RB (eds) Ionizing radiation damage to DNA Molecular aspects. Wiley-Liss, New York, pp 43-50... 

However, the location and concentration of the radicals stabilized at 77 K in /-irradiated DNA indicate that considerable charge and spin transfer occurs after the original ionizations. ° Because there is substantial evidence that electron-loss radicals are a significant source of strand breaks, ° the processes that lead to these radicals at 77 K must be understood if the origins of radiation-induced strand breaks are to be elucidated. In addition, even in those circumstances in which strand breaks do not result from an electron-loss damage site, the site may be part of a localized multiply damaged site (MDS), for which normal cellular DNA repair mechanisms are impaired. 

Thus, a single track may form a multiply damaged site (MDS) and such a site can result in a biologically unrepairable strand break on DNA. However, if, in such a cluster, several holes were to be funneled into a single guanine base (Scheme 3), a protective effect would result because only one damaged base would form from four proximate potential damage sites. Thus, the reactions in Scheme 3 may be operative as a radiation protective process even at low doses. 

Kozmin SG, Sedletska Y, Reynaud-Angelin A, Gasparutto D, Sage E. The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/ incision at base damage in eukaryotic cells. Nucleic Acids Res. 2009 37 1767-1777. 

Eot-Houlller G., Eon-Marchais S., Gasparutto D., Sage E., Processing of a complex multiply damaged DNA site by human cell extracts and purified repair proteins, Nucleic Acids Res., 2005, 33,260-271. 

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