Conformational polymorphysm of G-rich fragments of DNA Alu-repeats. II. The putative role of G-quadruplex structures in genomic rearrangements
- Authors: Varizhuk A.M.1, Sekridova A.V.1, Tankevich M.V.1, Podgorsky V.S.1, Smirnov I.P.1, Pozmogova G.E.1
-
Affiliations:
- Federal Research and Clinical Center of Physical-Chemical Medicine
- Issue: Vol 11, No 2 (2017)
- Pages: 146-153
- Section: Article
- URL: https://journals.rcsi.science/1990-7508/article/view/197755
- DOI: https://doi.org/10.1134/S1990750817020093
- ID: 197755
Cite item
Abstract
Three evolutionary conserved (G-rich) sites of Alu repeats (PQS2, PQS3, and PQS4) could form in vitro stable inter- and intramolecular G-quadruplexes (GQs). Structures and topologies of these GQs were elucidated using spectral methods. The study of self-association of G-rich Alu fragments performed using a FRET-based method revealed dimeric GQ formation from two distally located sites (PQS2)2, (PQS3)2 or PQS2−PQS3 within one extended single stranded DNA. Using DOSY NMR, AFM microscopy and differential CD spectroscopy it has been demonstrated that oligomer PQS4 (folded into a parallel intramolecular GQ) forms stacks of quadruplexes stabilized by stacking interactions of external G-tetrads. Comparative analysis of the properties of various GQs suggests involvement of two universal general mechanisms of GQ-dependent genomic rearrangements: (i) formation of dimeric GQs from fragments of different molecules; (ii) formation of GQ-GQ-stacks from pre-folded intramolecular parallel GQs from different strands. Thus, association of G-rich Alu motifs with sensitivity to double-strand breaks and rearrangements may be attributed not to structural features of G-rich Alu fragments, but also to their high abundance.
About the authors
A. M. Varizhuk
Federal Research and Clinical Center of Physical-Chemical Medicine
Email: pozmge@gmail.com
Russian Federation, ul. Malaya Pirogovskaya, 1a, Moscow, 119435
A. V. Sekridova
Federal Research and Clinical Center of Physical-Chemical Medicine
Email: pozmge@gmail.com
Russian Federation, ul. Malaya Pirogovskaya, 1a, Moscow, 119435
M. V. Tankevich
Federal Research and Clinical Center of Physical-Chemical Medicine
Email: pozmge@gmail.com
Russian Federation, ul. Malaya Pirogovskaya, 1a, Moscow, 119435
V. S. Podgorsky
Federal Research and Clinical Center of Physical-Chemical Medicine
Email: pozmge@gmail.com
Russian Federation, ul. Malaya Pirogovskaya, 1a, Moscow, 119435
I. P. Smirnov
Federal Research and Clinical Center of Physical-Chemical Medicine
Email: pozmge@gmail.com
Russian Federation, ul. Malaya Pirogovskaya, 1a, Moscow, 119435
G. E. Pozmogova
Federal Research and Clinical Center of Physical-Chemical Medicine
Author for correspondence.
Email: pozmge@gmail.com
Russian Federation, ul. Malaya Pirogovskaya, 1a, Moscow, 119435
Supplementary files
