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

Kumari, Nitu and Vartak, Supriya V and Dahal, Sumedha and Kumari, Susmita and Desai, Sagar S and Gopalakrishnan, Vidya and Choudhary, Bibha and Raghavan, Sathees C (2019) G-quadruplex Structures Contribute to Differential Radiosensitivity of the Human Genome. In: ISCIENCE, 21 . pp. 288-307.

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Official URL: https://dx.doi.org/10.1016/j.isci.2019.10.033

Abstract

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.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to CELL PRESS
Keywords: DOUBLE-STRAND BREAKS; MAJOR BREAKPOINT REGION; DNA-DAMAGE RESPONSE; WERNER-SYNDROME PROTEIN; HOMOLOGOUS RECOMBINATION; RECQ HELICASES; RADIATION; REPAIR; PROMOTER; INSTABILITY
Department/Centre: Division of Biological Sciences > Biochemistry
Depositing User: Id for Latest eprints
Date Deposited: 02 Jan 2020 06:11
Last Modified: 02 Jan 2020 06:11
URI: http://eprints.iisc.ac.in/id/eprint/64266

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