Conformational polymorphysm of G-rich fragments of DNA ALU-repeats. I. Potential noncanonical structures

Sekridova A.V.1, Varizhuk A.M.1, Tatarinova O.N.1, Severov V.V.1, Barinov N.A.1, Smirnov I.P.1, Lazarev V.N.1, Klinov D.V.1, Pozmogova G.E.1

1. Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20166205535      PubMed Id: 27797328
Year: 2016  Volume: 62  Issue: 5  Pages: 535-543
In this paper, we report results of systematic studies of conformational polymorphism of G-rich DNA fragments from Alu repeats. Alu retrotransposones are primate-specific short interspersed elements. Using the Alu sequence from the prooncogen bcl2 intron and the consensus AluSx sequence as representative examples, we determined characteristic Alu sites that are capable of adopting G-quadruplex (GQ) conformations (i.e., potential quadruplex sites – PQSAlu), and demonstrated by bioinformatics methods that those sites are Alu-specific in the human genome. Genomic frequencies of PQSAlu were assessed (~1/10000 b.p.). The sites were found to be characteristic of young (active) Alu families (Alu-Y). A recombinant DNA sequence bearing the Alu element from the human bcl2 gene (304 b.p.) and its PQS-mutant (Alu-PQS) were constructed. The formation of noncanonical structures in Alubcl2 dsDNA and the absence of such structures in the case of Alu-PQS were shown using DMS-footprinting and AFM microscopy. Expression vectors bearing wild-type and mutant Alu insertions in the promoter regions were obtained, and the effects of these insertions on the expression of the reporter gene in НЕК293 and HeLa cell lines were compared. Our findings on the spatial organization of Alu repeats may provide insight into the mechanisms of genomic rearrangements which underlie many oncological and neurodegenerative diseases.
Download PDF:  
Keywords: G-quadruplex DNA, Alu-repeats, dynamics of DNA secondary structures

Sekridova, A. V., Varizhuk, A. M., Tatarinova, O. N., Severov, V. V., Barinov, N. A., Smirnov, I. P., Lazarev, V. N., Klinov, D. V., Pozmogova, G. E. (2016). Conformational polymorphysm of G-rich fragments of DNA ALU-repeats. I. Potential noncanonical structures. Biomeditsinskaya Khimiya, 62(5), 535-543.
This paper is also available as the English translation: 10.1134/S1990750817010097
 2024 (vol 70)
 2023 (vol 69)
 2022 (vol 68)
 2021 (vol 67)
 2020 (vol 66)
 2019 (vol 65)
 2018 (vol 64)
 2017 (vol 63)
 2016 (vol 62)
 2015 (vol 61)
 2014 (vol 60)
 2013 (vol 59)
 2012 (vol 58)
 2011 (vol 57)
 2010 (vol 56)
 2009 (vol 55)
 2008 (vol 54)
 2007 (vol 53)
 2006 (vol 52)
 2005 (vol 51)
 2004 (vol 50)
 2003 (vol 49)