MTA-DE Momentum, Genome Architecture and Recombination Research Group, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary.
DNA Repair (Amst). 2019 Dec;84:102642. doi: 10.1016/j.dnarep.2019.102642. Epub 2019 Jul 6.
Unravelling the origin of genetic alterations from point mutations to chromosomal rearrangements was greatly enhanced by the discovery of RNA-DNA hybrids (R-loops) that behave as hotspots of genomic instability in a variety of organisms. Current models suggest that uncontrolled R-loops are a hazard to genome integrity, therefore, identifying proteins that are involved in recognising and signalling R-loop structures are of key importance. Herein we analysed key RNA-DNA hybrid binding proteins in humans taking advantage of large-scale gene expression, survival rate, and drug-sensitivity data from cancer genomics databases. We show that expression of RNA-DNA hybrid binding proteins in various cancer types is associated with survival and may have contrasting outcomes in responding to therapeutic treatments. Based on the revealed pharmacogenomic landscape of human RNA-DNA hybrid binding proteins, we propose that R-loops and R-loop binding proteins are potentially relevant new epigenetic markers and therapeutic targets in multiple cancers.
从点突变到染色体重排，RNA-DNA 杂交（R 环）的发现极大地揭示了遗传改变的起源，它在多种生物中表现为基因组不稳定性的热点。目前的模型表明，不受控制的 R 环对基因组完整性是一种危害，因此，鉴定参与识别和信号 R 环结构的蛋白质至关重要。在这里，我们利用癌症基因组数据库中的大规模基因表达、存活率和药物敏感性数据，分析了人类中关键的 RNA-DNA 杂交结合蛋白。我们表明，各种癌症类型中 RNA-DNA 杂交结合蛋白的表达与存活率相关，并可能对治疗反应产生相反的结果。基于揭示的人类 RNA-DNA 杂交结合蛋白的药物基因组景观，我们提出 R 环和 R 环结合蛋白可能是多种癌症中潜在的新表观遗传标记和治疗靶点。
