Nicasio-Collazo Luz Adriana, Delgado-González Alexandra, Castañeda-Priego Ramón, Hernández-Lemus Enrique
Division of Sciences and Engineering, University of Guanajuato, León, Mexico.
Division of Sciences and Engineering, University of Guanajuato, León, Mexico
J R Soc Interface. 2014 Nov 6;11(100):20140827. doi: 10.1098/rsif.2014.0785.
DNA damage is one of the mechanisms of mutagenesis. Sequence integrity may be affected by the action of thermal changes, chemical agents, both endogenous and exogenous, and other environmental issues. Abnormally high mutation rates are referred to as genomic instability: a phenomenon closely related to the onset of cancer. Mutant genotypes may be able to confer some kind of selective advantage on subclonal cell populations, leading them to multiply until dominance in a localized tissue environment that later becomes the tumour. Cellular stress, especially that of oxidative and ionic nature, is a recognized trigger for DNA-damaging processes. A physico-chemical model has shown that high hysteresis rates in DNA denaturation curves may be indicative of dissipative processes inducing DNA damage, thus potentially leading to uncontrolled mutagenesis and genome instability. We here study selectively to what extent this phenomenon may occur by analysing the sequence length and composition effects on the thermodynamic behaviour and the presence of hysteresis in pressure-driven DNA denaturation; pronounced hysteresis in the denaturation/renaturation curves may indicate thermal susceptibility to DNA damage. In particular, we consider highly mutated regions of the genome characterized in diffuse large B-cell lymphoma on a recent whole exome next-generation sequencing effort.
DNA损伤是诱变的机制之一。序列完整性可能会受到热变化、化学物质（包括内源性和外源性）以及其他环境因素作用的影响。异常高的突变率被称为基因组不稳定：这是一种与癌症发生密切相关的现象。突变基因型可能能够赋予亚克隆细胞群体某种选择性优势，导致它们增殖，直至在局部组织环境中占据主导地位，随后该组织环境会发展成肿瘤。细胞应激，尤其是氧化应激和离子应激，是公认的引发DNA损伤过程的因素。一个物理化学模型表明，DNA变性曲线中的高滞后率可能表明存在诱导DNA损伤的耗散过程，从而可能导致不受控制的诱变和基因组不稳定。我们在此通过分析序列长度和组成对压力驱动的DNA变性的热力学行为和滞后现象的影响，来选择性地研究这种现象可能发生的程度；变性/复性曲线中明显的滞后现象可能表明DNA对热损伤敏感。特别是，我们考虑了在最近一次全外显子组下一代测序研究中确定的弥漫性大B细胞淋巴瘤基因组的高度突变区域。
