title: What Makes Telomeres Unique?
abstract: Telomeres are repetitive nucleotide sequences, which are essential for protecting the termini of chromosomes. Thousands of such repetitions are necessary to maintain the stability of the whole chromosome. Several similar repeated telomeric sequences have been found in different species, but why has nature chosen them? What features do telomeres have in common? In this article, we study the physical properties of human-like (TTAGGG), plant (TTTAGG), insect (TTAGG), and Candida guilermondi (GGTGTAC) telomeres in comparison with seven control, nontelomeric sequences. We used steered molecular dynamics with the nucleic acid united residue (NARES) coarse-grained force field, which we compared with the all-atom AMBER14 force field and experimental data. Our results reveal important features in all of the telomeric sequences, including their exceptionally high mechanical resistance and stability to untangling and stretching, compared to those of nontelomeric sequences. We find that the additional stability of the telomeres comes from their ability to form triplex structures and wrap around loose chains of linear DNA by regrabbing the chain. We find that, with slower pulling speed, regrabbing and triplex formation is more frequent. We also found that some of the sequences can form triplexes experimentally, such as TTTTTCCCC, and can mimic telomeric properties.
authors.affiliation: Chemistry Department, University of Gdańsk , Wita Stwosza 63, Gdańsk 80-308, Poland.
authors.forename: Adam K
authors.identifier: 0000-0002-2426-3644
authors.initials: AK
authors.lastname: Sieradzan
authors.affiliation: Chemistry Department, University of Gdańsk , Wita Stwosza 63, Gdańsk 80-308, Poland.|Institute of Physics, Polish Academy of Sciences , Aleja Lotnikow 32/46, PL-02668 Warsaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Krupa
authors.affiliation: Department of Chemistry, Cambridge University , Lensfield Road, Cambridge CB2 1EW, U.K.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wales
mesh_terms: D000818:Animals; D001483:Base Sequence; D001669:Biochemical Phenomena; D002175:Candida; D004247:DNA / Q000737:chemistry*; D006801:Humans; D007313:Insecta; D055595:Mechanical Phenomena; D056004:Molecular Dynamics Simulation; D010944:Plants; D016615:Telomere / Q000737:chemistry*
chemical_list: D004247:DNA