Morales J C, Kool E T
Department of Chemistry, University of Rochester, New York 14627, USA.
Nat Struct Biol. 1998 Nov;5(11):950-4. doi: 10.1038/2925.
DNA polymerase enzymes make an error only once per 10(4)-10(5) initial nucleotide insertions during DNA replication. Most currently held models of this high fidelity cite the hydrogen bonds between complementary pyrimidines and purines as a critical controlling factor. Testing this has been difficult, however, since standard molecular strategies for blocking or removing polar hydrogen-bonding groups cause changes to size and shape as well as hydrogen bonding ability. One answer to this problem is the use of nonpolar molecules that mimic the shape of natural DNA bases. Here we show that a non-hydrogen-bonding shape mimic for adenine is replicated efficiently and selectively against a nonpolar shape mimic for thymine. The results establish that hydrogen bonds in a base pair are not absolutely required for efficient nucleotide insertion. This adds support to the idea that shape complementarity may play as important a role in replication as base-base hydrogen bonds.
DNA聚合酶在DNA复制过程中，每10⁴ - 10⁵个初始核苷酸插入中仅出现一次错误。目前大多数关于这种高保真度的模型都认为互补嘧啶和嘌呤之间的氢键是关键控制因素。然而，对此进行测试一直很困难，因为用于阻断或去除极性氢键基团的标准分子策略会导致大小、形状以及氢键结合能力的改变。解决这个问题的一个办法是使用模仿天然DNA碱基形状的非极性分子。在此我们表明，一种对腺嘌呤的非氢键结合形状模拟物能够高效且选择性地针对胸腺嘧啶的非极性形状模拟物进行复制。结果表明，碱基对中的氢键并非有效核苷酸插入绝对必需的。这为形状互补性在复制中可能与碱基间氢键发挥同样重要作用的观点提供了支持。
