Ivarie R
Department of Genetics, University of Georgia, Athens 30602.
Nucleic Acids Res. 1987 Dec 10;15(23):9975-83. doi: 10.1093/nar/15.23.9975.
Evidence is summarized showing that thymine methyls are as important in the recognition of specific sequences by proteins as are the more widely recognized hydrogen bonding sites of bases in the major groove (1). Strongest evidence has come from experiments using functional group mutagenesis (2) in which thymines in a specific recognition sequence (e.g., promoters, operators and restriction sites) are replaced by oligonucleotide synthesis with methyl-free uracil or cytosine and 5-methylcytosine. Such experiments have shown that thymine methyls can provide contact points via van der Waals interactions with amino acid side chains of specific DNA binding proteins. Actual contact between a thymine methyl and carbons of a glutamine side chain has been observed in a cocrystal of the phage 434 repressor and its operator by X-ray analysis. The issue of why thymine occurs in DNA is discussed in light of these findings.
证据表明，胸腺嘧啶甲基在蛋白质识别特定序列方面与在大沟中碱基更广泛认可的氢键位点一样重要(1)。最有力的证据来自使用官能团诱变的实验(2)，其中特定识别序列（如启动子、操纵子和限制位点）中的胸腺嘧啶被无甲基的尿嘧啶或胞嘧啶以及5-甲基胞嘧啶通过寡核苷酸合成所取代。此类实验表明，胸腺嘧啶甲基可通过范德华相互作用与特定DNA结合蛋白的氨基酸侧链提供接触点。通过X射线分析，在噬菌体434阻遏物及其操纵子的共晶体中观察到了胸腺嘧啶甲基与谷氨酰胺侧链碳之间的实际接触。根据这些发现讨论了DNA中为何存在胸腺嘧啶的问题。
