1.

Anti-sense DNA d(GGCCCC)n expansions in C9ORF72 form i-motifs and protonated hairpins

In collaboration with the research group of prof. Janez Plavec from the Institute of Chemistry in Ljubljana, we investigated the topology of various lengths of the antisense (G2C4) hexanucleotide repeat. In contrast with the current assumptions, we have shown that the different lengths of the G2C4 DNA sequences can form i-motifs and protonated hairpins in conditions similar to the physiological and not only in highly acidic conditions. Physiological conditions were simulated with a suitable pH, the addition of potassium, and 40% PEG. In additional experiments we have shown that the presence of the two complementary chains of the repeat DNA (G4C2 and G2C4) G-quadruplexes and i-motifs were preferably formed, but not double-stranded helix DNA as expected.

COBISS.SI-ID: 29086759

2.

Characterization of DNA G-quadruplex species forming from C 9ORF72 G[sub]4 C[sub]2 expanded repeats associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration

Using nuclear magnetic resonance and circular dichroism spectroscopy we show that DNA G4C2 with varying number of repeats d(G4C2)n form planar guanine quartets characteristic of G-quadruplexes. Additionally, we show DNA G-quadruplexes can form inter- and intra-molecularly in either parallel or anti-parallel orientation, based on d(G4C2) sequence length. This potential structural heterogeneity of longer disease-relevant repeats should therefore be taken into account when studying their role in disease pathogenesis.

COBISS.SI-ID: 27972647