Conformational polymorphysm of G-rich fragments of DNA Alu-repeats. II. The putative role of G-quadruplex structures in genomic rearrangements


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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

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