G-quadruplex Structures Contribute to Differential Radiosensitivity of the Human Genome

• Published in: iScience Vol. 21; pp. 288 - 307
• Main Authors: Kumari, Nitu, Vartak, Supriya V., Dahal, Sumedha, Kumari, Susmita, Desai, Sagar S., Gopalakrishnan, Vidya, Choudhary, Bibha, Raghavan, Sathees C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.11.2019; Elsevier
• Subjects: Biochemistry; Biological Sciences; Cell Biology; Molecular Biology; Biological Sciences; Biochemistry; Molecular Biology; Cell Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.10.033

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. [Display omitted] •G4 DNA contributes to genome-wide radioprotection and is modulated by G4 resolvases•Radiation causes minimal damage at the G4 structures at telomeres•Formation of G4 DNA contributes toward differential radiosensitivity of human genome•Planar quartet of G4 DNA is shielded from IR-induced free radicals and thus DNA breaks Biological Sciences; Biochemistry; Molecular Biology; Cell Biology