DNA dynamics is likely to be a factor in the genomic nucleotide repeats expansions related to diseases.
DNA dynamics is likely to be a factor in the genomic nucleotide repeats expansions related to diseases.
复制标题
DOI：
10.1371/journal.pone.0019800
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Usheva A
中科院分区：
文献类型：
--
作者：
Alexandrov BS;Valtchinov VI;Alexandrov LB;Gelev V;Dagon Y;Bock J;Kohane IS;Rasmussen KØ;Bishop AR;Usheva A
Trinucleotide repeats sequences (TRS) represent a common type of genomic DNA motif whose expansion is associated with a large number of human diseases. The driving molecular mechanisms of the TRS ongoing dynamic expansion across generations and within tissues and its influence on genomic DNA functions are not well understood. Here we report results for a novel and notable collective breathing behavior of genomic DNA of tandem TRS, leading to propensity for large local DNA transient openings at physiological temperature. Our Langevin molecular dynamics (LMD) and Markov Chain Monte Carlo (MCMC) simulations demonstrate that the patterns of openings of various TRSs depend specifically on their length. The collective propensity for DNA strand separation of repeated sequences serves as a precursor for outsized intermediate bubble states independently of the G/C-content. We report that repeats have the potential to interfere with the binding of transcription factors to their consensus sequence by altered DNA breathing dynamics in proximity of the binding sites. These observations might influence ongoing attempts to use LMD and MCMC simulations for TRS–related modeling of genomic DNA functionality in elucidating the common denominators of the dynamic TRS expansion mutation with potential therapeutic applications.
登录
查看更多内容
影响因子：
14.9
作者：
Greene E;Mahishi L;Entezam A;Kumari D;Usdin K
通讯作者：
Usdin K
影响因子：
14.9
作者：
Alexandrov BS;Gelev V;Monisova Y;Alexandrov LB;Bishop AR;Rasmussen KØ;Usheva A
通讯作者：
Usheva A
影响因子：
64.8
作者：
Kovtun, Irina V.;Liu, Yuan;McMurray, Cynthia T.
通讯作者：
McMurray, Cynthia T.
影响因子：
3.7
作者：
Cheli Y;Williams SA;Ballotti R;Nugent DJ;Kunicki TJ
通讯作者：
Kunicki TJ
影响因子：
14.9
作者：
Rindler PM;Bidichandani SI
通讯作者：
Bidichandani SI