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Vectorial folding of telomere overhang promotes higher accessibility.
Paul, Tapas; Opresko, Patricia L; Ha, Taekjip; Myong, Sua.
Afiliación
  • Paul T; Department of Biophysics, Johns Hopkins University, Baltimore, MD21218, USA.
  • Opresko PL; Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, and UPMC Hillman Cancer Center, Pittsburgh, PA15213, USA.
  • Ha T; Department of Biophysics, Johns Hopkins University, Baltimore, MD21218, USA.
  • Myong S; Physics Frontier Center (Center for Physics of Living Cells), University of Illinois, 1110 W. Green St., Urbana, IL 61801, USA.
Nucleic Acids Res ; 50(11): 6271-6283, 2022 06 24.
Article en En | MEDLINE | ID: mdl-35687089
Human telomere overhang composed of tandem repeats of TTAGGG folds into G-quadruplex (G4). Unlike in an experimental setting in the test tube in which the entire length is allowed to fold at once, inside the cell, the overhang is expected to fold as it is synthesized directionally (5' to 3') and released segmentally by a specialized enzyme, the telomerase. To mimic such vectorial G4 folding process, we employed a superhelicase, Rep-X which can unwind DNA to release the TTAGGG repeats in 5' to 3' direction. We demonstrate that the folded conformation achieved by the refolding of full sequence is significantly different from that of the vectorial folding for two to eight TTAGGG repeats. Strikingly, the vectorially folded state leads to a remarkably higher accessibility to complementary C-rich strand and the telomere binding protein POT1, reflecting a less stably folded state resulting from the vectorial folding. Importantly, our study points to an inherent difference between the co-polymerizing and post-polymerized folding of telomere overhang that can impact telomere architecture and downstream processes.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Telómero / G-Cuádruplex Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Telómero / G-Cuádruplex Límite: Humans Idioma: En Revista: Nucleic Acids Res Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos