Department of Radiology, University of California at San Diego, La Jolla, California 92093-0610, USA.
Radiat Res. 2012 Feb;177(2):152-63. doi: 10.1667/rr2812.1. Epub 2011 Nov 21.
The DNA-binding proteins that are present in chromatin significantly affect the sensitivity of cells to ionizing radiation and to the radiation chemistry of DNA damage. The interaction between protein and DNA modifies the radiation chemistry of the latter. To model these processes, we have examined the effects of ionizing radiation on the minichromosome form of SV40 (which contains histone proteins arranged in nucleosomes) and also on plasmid DNA in the presence of lysozyme. Although high concentrations of lysozyme can bring about an extensive radioprotection by condensation of the plasmid, at lower levels it still produces significant radioprotective effects under conditions where this associative phase separation does not take place. The presence of histones or of lysozyme decreases the yield of modified guanines produced by ionizing radiation. Comparison with previous observations made with oligopeptides suggests that the mechanism responsible is electron donation to guanyl radicals in the DNA by tryptophan and tyrosine residues in the proteins. However, there was no evidence for DNA-protein crosslink formation.
存在于染色质中的 DNA 结合蛋白会显著影响细胞对电离辐射以及 DNA 损伤的辐射化学的敏感性。蛋白质与 DNA 的相互作用会改变后者的辐射化学性质。为了模拟这些过程，我们研究了电离辐射对 SV40 微小染色体形式（其中包含组蛋白，这些组蛋白排列在核小体中）的影响，以及在溶菌酶存在下对质粒 DNA 的影响。尽管高浓度的溶菌酶可以通过质粒的凝聚来实现广泛的辐射防护，但在较低浓度下，即使在这种缔合相分离没有发生的情况下，它仍然会产生显著的辐射防护效果。组蛋白或溶菌酶的存在会降低由电离辐射产生的修饰鸟嘌呤的产量。与以前用寡肽进行的观察结果进行比较表明，负责这一机制的是蛋白质中的色氨酸和酪氨酸残基向 DNA 中的鸟苷自由基提供电子。然而，没有证据表明形成了 DNA-蛋白质交联。
