Derks Kasper W J, Hoeijmakers Jan H J, Pothof Joris
Department of Genetics, Netherlands Toxicogenomics Center, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Department of Genetics, Netherlands Toxicogenomics Center, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
DNA Repair (Amst). 2014 Jul;19:214-20. doi: 10.1016/j.dnarep.2014.03.008. Epub 2014 Apr 30.
The emergence of high density technologies monitoring the genome, transcriptome and proteome in relation to genotoxic stress have tremendously enhanced our knowledge on global responses and dynamics in the DNA damage response, including its relation with cancer and aging. Moreover, '-omics' technologies identified many novel factors, their post-translational modifications, pathways and global responses in the cellular response to DNA damage. Based on omics, it is currently estimated that thousands of gene(product)s participate in the DNA damage response, recognizing complex networks that determine cell fate after damage to the most precious cellular molecule, DNA. The development of next generation sequencing technology and associated specialized protocols can quantitatively monitor RNA and DNA at unprecedented single nucleotide resolution. In this review we will discuss the contribution of omics technologies and in particular next generation sequencing to our understanding of the DNA damage response and the future prospective of next generation sequencing, its single cell application and omics dataset integration in unraveling intricate DNA damage signaling networks.
与基因毒性应激相关的监测基因组、转录组和蛋白质组的高密度技术的出现，极大地增进了我们对DNA损伤反应中的全局反应和动态变化的了解，包括其与癌症和衰老的关系。此外，“组学”技术还鉴定出许多新因子、它们的翻译后修饰、细胞对DNA损伤反应中的信号通路和全局反应。基于组学，目前估计有成千上万的基因（产物）参与DNA损伤反应，识别出在对最珍贵的细胞分子DNA造成损伤后决定细胞命运的复杂网络。下一代测序技术及相关专业方案的发展能够以前所未有的单核苷酸分辨率对RNA和DNA进行定量监测。在本综述中，我们将讨论组学技术，特别是下一代测序技术，对我们理解DNA损伤反应的贡献，以及下一代测序技术在揭示复杂的DNA损伤信号网络中的单细胞应用和组学数据集整合方面的未来前景。
