Abstract :
[en] Non-canonical nucleic acid structures, such as G-quadruplexes, have recently attracted significant research efforts for their potential roles in the regulation of numerous biological processes [1]. There is now evidence that these specific nucleic acid structures modulate gene expression. The formation of hybrid DNA/RNA G-quadruplexes (HQs) where each strand contribute to the structure with two series of guanines, was recently found to form in DNA during transcription [2]. It has been evidenced that the HQ formation competes with intramolecular G-quadruplexe motifs (DQ) and plays a major role in regulating transcription [3]. Given their very recent discovery, only a few studies on the formation of these hybrid structures have been conducted so far. However, the knowledge of their mechanism of formation and their detailed structure is important for understanding their biological function, as well as for manipulating gene expression by targeting HQs.
We propose here to study these hybrid DNA/RNA G-quadruplexe structures by AFM-based single molecule force spectroscopy to obtain detailed information, at the single molecule level, on their formation mechanism and dynamics, their structure and interactions that govern the complex, their mechanical stability and their lability.
References
[1] M. L. Bochman, K. Paeschke, V. A. Zakian, Nat. Rev. Genet., 2012, 13, 770-780.
[2] K. W. Zheng, S. Xiao, J. Q. Liu, J. Y. Zhang, Y. H. Hao, Z. Tan, Nucleic Acids Res., 2013, 41, 5533-5541.
[3] R.-Y. Wu, K.-W Zheng, J.-Y. Zhang, Y.-H. Hao, Z. Tan, Angew. Chem. Int. Ed., 2015, 54, 2477-2481.
