In vivo guanine quadruplex structure dynamics and role in genome maintenance in Deinococcus radiodurans

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The paper investigates how guanine quadruplex (G4) DNA structures form and change in vivo in the radioresistant bacterium Deinococcus radiodurans under DNA-damaging conditions, using assays including thioflavin T staining and anti-DNA quadruplex antibodies, as well as in vitro characterization of G4 motifs with different cations. The authors report that in vivo G4 structures increase and show dynamic responses, especially after gamma radiation, and that G4 binding drugs during the post-irradiation recovery period arrest G4 dynamics and delay DNA repair. They also find that magnesium supports stable G4 formation while manganese destabilizes it, and that deleting the G4 helicase RecQ leads to accumulation of more G4 structures and genome instability. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Guanine quadruplex (G4) structures are secondary structures formed in nucleic acids that are rich in guanine bases. G4 structures regulate various cellular processes both in eukaryotes and prokaryotes. Deinococcus radiodurans , an extremophile show sensitivity to ionizing radiation in the presence of G4 binding ligands during the post-irradiation recovery period (PIR). Putative G4 motifs positioned at different locations on the genes fold into different topologies in vitro in the presence of monovalent cations while divalent cation Mg +2 supported the stable G4 formation but Mn +2 destabilizes the G4 structures. Thioflavin T and anti-DNA quadruplex antibodies detected the in vivo formation and dynamics of G4 structure in response to various DNA damaging agents, more in the presence of gamma radiation treatment. G4 binding drugs during PIR arrested the G4 structure dynamics and delayed the DNA repair process. Further, the absence of G4 helicase, RecQ resulted in the accumulation of more G4 structures and genome instability. All these results indicate that the guanine quadruplex structure formation increases in response to cellular stress and G4s are crucial for stable genome maintenance in Deinococcus radiodurans .
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Abstract Guanine quadruplex (G4) structures are secondary structures formed in nucleic acids that are rich in guanine bases. G4 structures regulate various cellular processes both in eukaryotes and prokaryotes. Deinococcus radiodurans, an extremophile show sensitivity to ionizing radiation in the presence of G4 binding ligands during the post-irradiation recovery period (PIR). Putative G4 motifs positioned at different locations on the genes fold into different topologies in vitro in the presence of monovalent cations while divalent cation Mg+2 supported the stable G4 formation but Mn+2 destabilizes the G4 structures. Thioflavin T and anti-DNA quadruplex antibodies detected the in vivo formation and dynamics of G4 structure in response to various DNA damaging agents, more in the presence of gamma radiation treatment. G4 binding drugs during PIR arrested the G4 structure dynamics and delayed the DNA repair process. Further, the absence of G4 helicase, RecQ resulted in the accumulation of more G4 structures and genome instability. All these results indicate that the guanine quadruplex structure formation increases in response to cellular stress and G4s are crucial for stable genome maintenance in Deinococcus radiodurans. Competing Interest Statement The authors have declared no competing interest.

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