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

Summary: 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 r...

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Bibliographic Details
Main Authors: Nitu Kumari, Supriya V. Vartak, Sumedha Dahal, Susmita Kumari, Sagar S. Desai, Vidya Gopalakrishnan, Bibha Choudhary, Sathees C. Raghavan
Format: Article
Language:English
Published: Elsevier 2019-11-01
Series:iScience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004219304134
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Summary:Summary: 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. : Biological Sciences; Biochemistry; Molecular Biology; Cell Biology Subject Areas: Biological Sciences, Biochemistry, Molecular Biology, Cell Biology
ISSN:2589-0042