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

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...

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Published iniScience 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
LanguageEnglish
Published United States Elsevier Inc 22.11.2019
Elsevier
Subjects
Biochemistry
Biological Sciences
Cell Biology
Molecular Biology
Biological Sciences
Biochemistry
Molecular Biology
Cell Biology
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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. [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
AbstractList 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, 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, 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. • 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
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
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
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.
Author Kumari, Nitu
Choudhary, Bibha
Raghavan, Sathees C.
Kumari, Susmita
Desai, Sagar S.
Vartak, Supriya V.
Dahal, Sumedha
Gopalakrishnan, Vidya
AuthorAffiliation 1 Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
2 Institute of Bioinformatics and Applied Biotechnology, Electronics City, Bangalore 560100, India
3 Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
4 Department of Zoology, St. Joseph’s College, Irinjalakkuda, Kerala, 680121, India
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  email: sathees@iisc.ac.in
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Snippet 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...
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SubjectTerms Biochemistry
Biological Sciences
Cell Biology
Molecular Biology
Title G-quadruplex Structures Contribute to Differential Radiosensitivity of the Human Genome
URI https://dx.doi.org/10.1016/j.isci.2019.10.033
https://www.ncbi.nlm.nih.gov/pubmed/31678912
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