G-Tract Length Shapes the Fate of G-Quadruplexes

Abstract

Guanine (G)-rich DNA sequences can form unusual secondary structures known as G-quadruplexes (or G4s). The stability of these structures, whose folding is mainly driven by the formation and stacking of G-quartets, is influenced by several factors, foremost among them the nature of the sequence itself, particularly the nucleobases flanking the G-tracts, and the loops connecting them. A considerable effort has been devoted to understanding how the size, position, and composition of each loop and flanking sequences affect the stability of the resulting G4 fold. However, most of these studies have been restricted to sequences forming a three G-quartet G4 core. To better understand how the length of the G-tracts (from three to five Gs) and loops (from one to seven nucleotides) act in concert, we studied a set of 261 different sequences covering different possible combinations. A systematic biophysical analysis suggests that sequences with longer G-tracts tend to form more stable G4s, but also a mixture of species; it further shows that loop composition and position also influence the topology and stability of the resulting G4s. Collectively, this work provides an unprecedented view on how G4-forming sequences fold upon themselves and of the structural features that govern the stability of the resulting G4s.

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Cite

BibTeX RIS

BibTeX

@article{zhou2026gtract,
  title = {{G-Tract Length Shapes the Fate of G-Quadruplexes}},
  author = {Jiahang Zhou and Jianjun Xia and Petr Stadlbauer and Mingpan Cheng and Shijiong Wei and Xinrong Yan and Xinzhe Zhuang and Huangxian Ju and Jiří Šponer and Jean-Louis Mergny and David Monchaud and Jun Zhou},
  journal = {ACS Chemical Biology},
  year = {2026},
  month = oct,
  doi = {10.1021/acschembio.6c00664},
  url = {https://hal.science/hal-05844101v1},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - G-Tract Length Shapes the Fate of G-Quadruplexes
AU  - Jiahang Zhou
AU  - Jianjun Xia
AU  - Petr Stadlbauer
AU  - Mingpan Cheng
AU  - Shijiong Wei
AU  - Xinrong Yan
AU  - Xinzhe Zhuang
AU  - Huangxian Ju
AU  - Jiří Šponer
AU  - Jean-Louis Mergny
AU  - David Monchaud
AU  - Jun Zhou
PY  - 2026
DA  - 2026/10/29
JO  - ACS Chemical Biology
DO  - 10.1021/acschembio.6c00664
UR  - https://hal.science/hal-05844101v1
AB  - Guanine (G)-rich DNA sequences can form unusual secondary structures known as G-quadruplexes (or G4s). The stability of these structures, whose folding is mainly driven by the formation and stacking of G-quartets, is influenced by several factors, foremost among them the nature of the sequence itself, particularly the nucleobases flanking the G-tracts, and the loops connecting them. A considerable effort has been devoted to understanding how the size, position, and composition of each loop and flanking sequences affect the stability of the resulting G4 fold. However, most of these studies have been restricted to sequences forming a three G-quartet G4 core. To better understand how the length of the G-tracts (from three to five Gs) and loops (from one to seven nucleotides) act in concert, we studied a set of 261 different sequences covering different possible combinations. A systematic biophysical analysis suggests that sequences with longer G-tracts tend to form more stable G4s, but also a mixture of species; it further shows that loop composition and position also influence the topology and stability of the resulting G4s. Collectively, this work provides an unprecedented view on how G4-forming sequences fold upon themselves and of the structural features that govern the stability of the resulting G4s.
SN  - 1554-8929
SN  - 1554-8937
ER  -

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