Journal
ELIFE
Volume 6, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.26884
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Funding
- Agence Nationale de la Recherche [ANR-12-BSV6-0002-01, ANR-14-CE35-0003-01]
- Ministry of Education - Singapore [MOE2012-T3-1-001]
- Nanyang Technological University
- Fondation ARC pour la Recherche sur le Cancer
- MENRT Fellowship Doctoral fellowship
- Agence Nationale de la Recherche (ANR) [ANR-12-BSV6-0002, ANR-14-CE35-0003] Funding Source: Agence Nationale de la Recherche (ANR)
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G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G-rich nucleic acids in vitro, but the sequence and structural features dictating their formation and function in vivo remains uncertain. Here we report a structure-function analysis of the complex hCEB1 G4-forming sequence. We isolated four G4 conformations in vitro, all of which bear unusual structural features: Form 1 bears a V-shaped loop and a snapback guanine; Form 2 contains a terminal G-triad; Form 3 bears a zero-nucleotide loop; and Form 4 is a zero-nucleotide loop monomer or an interlocked dimer. In vivo, Form 1 and Form 2 differently account for 2/3rd of the genomic instability of hCEB1 in two G4-stabilizing conditions. Form 3 and an unidentified form contribute to the remaining instability, while Form 4 has no detectable effect. This work underscores the structural polymorphisms originated from a single highly G-rich sequence and demonstrates the existence of non-canonical G4s in cells, thus broadening the definition of G4 forming sequences.
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