Background: DNA, the genetic material of most of the organisms, is the crucial element of life. Integrity of DNA needs to be maintained for transmission of genetic material from one generation to another. All organisms are constantly challenged by the environmental conditions which can lead to the induction of DNA damage. Ionizing radiation (IR) has been known to induce DNA damage and IR sensitivity varies among different organisms. The causes for differential radiosensitivity among various organisms have not been studied in great detail.

Scope of review: We discuss DNA secondary structure formation, GC content of the genome, role of G-quadruplex formation, and its relationship with radiosensitivity of the genome.

Major conclusion: In Deinococcus radiodurans, the bacterium that exhibits maximum radio resistance, multiple G-quadruplex forming motifs are reported. In human cells, G-quadruplex formation led to differential radiosensitivity. In this article, we have discussed, the role of secondary DNA structure formation like G-quadruplex in shielding the genome from radiation and its implications in understanding evolution of radio protective effect of an organism. We also discuss role of GC content and its correlation with radio resistance.

General significance: This review provides an insight into the role of G-quadruplexes in providing differential radiosensitivity at different site of the genome and in different organisms. It further discusses the possibility of higher GC content contributing towards reduced radiosensitivity in different organisms, evolution of radiosensitivity, and regulation of multiple cellular processes.