Phylogenetically diverged structural motifs in telomeric DNA

M. Gajarský^1,2, M. Lenarčič Živković³, K. Beková¹, J. Plavec³, L. Trantírek¹

¹Central European Institute of Technology, Masaryk University, Brno, Czech Republic

²National Centre for Biomolecular Research, Masaryk University, Brno, Czech Republic

³Kemijski institute - National Institute of Chemistry, Ljubljana, Slovenia

martin.gajarsky@ceitec.muni.cz

Telomeres, specialized nucleoprotein complexes, cap and protect the physical ends of chromosomes and are essential for genome stability. Telomeric DNA buffers the end replication problem caused by the DNA polymerases inability to copy the very end of the molecule.[1] In vast majority of somatic cells this chromosome shortening inevitably leads to cell death, however, in germ, stem, and cancer cells it is countered by telomerase, or ALT pathway (Alternative Lengthening of Telomeres).[2,3]

Full understanding of biological role and functioning of telomeres is therefore a crucial part of cancer and ageing research. Our focus is on structural behaviour of telomeric DNA. Its typical features in all eukaryotic kingdoms are single stranded, guanine rich 3’-overhang, conserved repeats of primary sequence (T_2-4AG_2-3) and inherent ability to adopt a non-canonical DNA structure, G-quadruplex.[4]

Our study focuses on the aberrant examples in phylogenetic tree, in hope to better understand conserved characteristics crucial for proper functioning of telomeres. Despite apparent strong conservation of DNA primary sequence in telomeric repeats and capacity of G-quadruplex formation present in almost all species (see Figure 1), our data suggest that the crucial characteristic of telomeric DNA that is preserved throughout evolution is not the primary sequence, nor the G-quadruplex folding, but the ability to form various, stable, non-canonical structures in general. Considering abundance of unusual non-canonical motifs recently discovered on telomeric sequences, telomeres are also an extremely useful source of information about structural behaviour of the DNA molecule for future biotechnological, drug-target, or aptamer research.

Figure 1. Non canonical DNA structures in telomeres of eukaryotic kingdoms.

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2. Greider, C. W.; Blackburn, E. H. Nature 1989, 337 (6205), 331.
3. Bryan, T. M.; Englezou, A.; Gupta, J.; Bacchetti, S.; Reddel, R. R. EMBO J. 1995, 14 (17), 4240–4248.
4. Tran, P. L. T.; Mergny, J.-L.; Alberti, P. Nucleic Acids Res. 2011, 39 (8), 3282–3294

This research was supported by the grant from Czech Science Foundation (19-26041X), by the grant from Ministry of Health of the Czech Republic (NV19-08-00450), and by the project SYMBIT (CZ.02.1.01/0.0/0.0/15_003/0000477) funded by the European Regional Development Fund and Ministry of Education, Youth, and Sports (MEYS) of the Czech Republic. MEYS is also acknowledged for its support of access to research infrastructure (CEITEC 2020 LQ1601; CIISB-LM2018127).