What Makes Telomeres Unique?

被引:14
作者
Sieradzan, Adam K. [1 ]
Krupa, Pawel [1 ,2 ]
Wales, David J. [3 ]
机构
[1] Univ Gdansk, Dept Chem, Wita Stwosza 63, PL-80952 Gdansk, Poland
[2] Polish Acad Sci, Inst Phys, Aleja Lotnikow 32-46, PL-02668 Warsaw, Poland
[3] Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England
基金
英国工程与自然科学研究理事会;
关键词
UNRES FORCE-FIELD; UNITED-RESIDUE MODEL; DOUBLE-STRAND BREAKS; MOLECULAR-DYNAMICS; COMPLEMENTARY STRANDS; DNA; PROTEIN; END; SIMULATIONS; PREDICTIONS;
D O I
10.1021/acs.jpcb.6b08780
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
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.
引用
收藏
页码:2207 / 2219
页数:13
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