DNA, the fundamental unit of human cell, generally exists in Watson-Crick base-paired B-DNA form. Often, DNA folds into non-B forms, such as four-stranded G-quadruplexes. It is generally believed that ionizing radiation (IR) induces DNA strand-breaks in a random manner. Here, we show that regions of DNA enriched in G-quadruplex structures are less sensitive to IR compared with B-DNA in vitro and inside cells. Planar G-quartet of G4-DNA is shielded from IR-induced free radicals, unlike single- and double-stranded DNA. Whole-genome sequence analysis and real-time PCR reveal that genomic regions abundant in G4-DNA are protected from radiation-induced breaks and can be modulated by G4 stabilizers. Thus, our results reveal that formation of G4 structures contribute toward differential radiosensitivity of the human genome.

DNA是人类细胞的基本单位，通常以Watson-Crick碱基配对的B-DNA形式存在。通常，DNA会折叠成非B形式，例如四链G-四链体。通常认为，电离辐射（IR）以随机方式诱导DNA链断裂。在这里，我们表明，与体外B-DNA相比，富含G-四链体结构的DNA区域对IR的敏感性较低。和细胞内部。与单链和双链DNA不同，G4-DNA的平面G四联体可抵御IR诱导的自由基。全基因组序列分析和实时PCR表明，富含G4-DNA的基因组区域受到辐射诱导的断裂的保护，并且可以由G4稳定剂调节。因此，我们的结果表明G4结构的形成有助于人类基因组的放射敏感性差异。