DNA bending propensity in the presence of base mismatches: implications for DNA repair.
DNA bending propensity in the presence of base mismatches: implications for DNA repair.
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存在碱基错配时的 DNA 弯曲倾向：对 DNA 修复的影响。
DOI：
10.1021/jp403127a
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Feig,Michael
中科院分区：
文献类型：
--
作者：
Sharma,Monika;Predeus,AlexanderV;Mukherjee,Shayantani;Feig,Michael
DNA弯曲被认为有助于最初识别错配的碱基进行修复。修复效率取决于错配类型和相邻核苷酸序列。我们已经研究了几种DNA双链体的弯曲，这些DNA双链体包含典型匹配：A：T和G：C;各种错配：A：A，A：C，G：A，G：G，G：T，C：C，C：T和T：T;以及双脱碱基位点：X：X。使用伞形取样产生DNA弯曲的自由能分布。与DNA弯曲相关的最高能量成本被观察到典型的匹配，而弯曲自由能较低的存在下的错配，与最低值的脱碱基位点。在所有的序列中，DNA双链体随着小沟的加宽而向大沟弯曲。对于同源双链体，观察到DNA弯曲通过平滑变形发生，而对于异源双链体，在强弯曲期间在错配位点观察到扭结。一般来说，嘧啶：嘧啶错配是最不稳定的，而嘌呤：嘌呤错配导致中间不稳定，嘌呤：嘧啶错配是最不稳定的。弯曲的难易程度与MutS对错配对的结合亲和力和随后的修复效率部分相关，表明固有的DNA弯曲倾向是错配识别的关键因素。
DNA bending is believed to facilitate the initial recognition of the mismatched base for repair. The repair efficiencies are dependent on both the mismatch type and neighboring nucleotide sequence. We have studied bending of several DNA duplexes containing canonical matches: A:T and G:C; various mismatches: A:A, A:C, G:A, G:G, G:T, C:C, C:T, and T:T; and a bis-abasic site: X:X. Free-energy profiles were generated for DNA bending using umbrella sampling. The highest energetic cost associated with DNA bending is observed for canonical matches while bending free energies are lower in the presence of mismatches, with the lowest value for the abasic site. In all of the sequences, DNA duplexes bend toward the major groove with widening of the minor groove. For homoduplexes, DNA bending is observed to occur via smooth deformations, whereas for heteroduplexes, kinks are observed at the mismatch site during strong bending. In general, pyrimidine:pyrimidine mismatches are the most destabilizing, while purine:purine mismatches lead to intermediate destabilization, and purine:pyrimidine mismatches are the least destabilizing. The ease of bending is partially correlated with the binding affinity of MutS to the mismatch pairs and subsequent repair efficiencies, indicating that intrinsic DNA bending propensities are a key factor of mismatch recognition.
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