Kathuria Preetleen, Sharma Purshotam, Wetmore Stacey D
Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, Alberta, T1K 3M4, Canada.
Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, Alberta, T1K 3M4, Canada
Nucleic Acids Res. 2015 Sep 3;43(15):7388-97. doi: 10.1093/nar/gkv701. Epub 2015 Jul 14.
Computational modeling is employed to provide a plausible structural explanation for the experimentally-observed differential global genome repair (GGR) propensity of the ALII-N(2)-dG and ALII-N(6)-dA DNA adducts of aristolochic acid II. Our modeling studies suggest that an intrinsic twist at the carcinogen-purine linkage of ALII-N(2)-dG induces lesion site structural perturbations and conformational heterogeneity of damaged DNA. These structural characteristics correlate with the relative repair propensities of AA-adducts, where GGR recognition occurs for ALII-N(2)-dG, but is evaded for intrinsically planar ALII-N(6)-dA that minimally distorts DNA and restricts the conformational flexibility of the damaged duplex. The present analysis on the ALII adduct model systems will inspire future experimental studies on these adducts, and thereby may extend the list of structural factors that directly correlate with the propensity for GGR recognition.
采用计算模型为实验观察到的马兜铃酸II的ALII-N(2)-dG和ALII-N(6)-dA DNA加合物的差异全局基因组修复（GGR）倾向提供合理的结构解释。我们的模型研究表明，ALII-N(2)-dG致癌物-嘌呤键处的内在扭曲会导致损伤位点的结构扰动和受损DNA的构象异质性。这些结构特征与AA加合物的相对修复倾向相关，其中ALII-N(2)-dG可发生GGR识别，但对于本质上呈平面状、对DNA扭曲最小且限制受损双链体构象灵活性的ALII-N(6)-dA则可避免GGR识别。对ALII加合物模型系统的当前分析将启发未来对这些加合物的实验研究，从而可能扩展与GGR识别倾向直接相关的结构因素列表。
Zotero 插件
