DNA Polymerases and Aminoacyl-tRNA Synthetases: Shared Mechanisms for Ensuring the Fidelity of Gene Expression
DNA Polymerases and Aminoacyl-tRNA Synthetases: Shared Mechanisms for Ensuring the Fidelity of Gene Expression
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DOI：
10.1021/bi801500z
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发表时间：
2008-11-11
期刊：
影响因子：
2.9
通讯作者：
Francklyn, Christopher S.
中科院分区：
文献类型：
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作者：
Francklyn, Christopher S.
DNA聚合酶和氨基酰基trna合成酶（ARSs）代表了在遗传信息从DNA到RNA再到蛋白质的转化中起关键作用的大酶家族。DNA聚合酶在基因组修复中进行复制和协作，而ars为蛋白质合成提供氨基酰化的tRNA前体。这两个家族的酶都面临着从化学相关分子池中选择同源小分子底物的共同挑战，在校对机制的帮助下实现高水平的歧视。本文综述了这两个重要系统的保真保护机制，并强调了它们的相似特征。DNA聚合酶和ars的共同特点是使用多结构域架构，将合成和校对功能分离到离散的结构域；利用诱导配合提高结合选择性；在化学层面上对保真度的强制；以及使用化学后纠错机制在一个离散的编辑域水解不正确的产物。这些后一种机制进一步具有共同的特性，即错误纠正涉及将错误结合的产物从合成位点转移到编辑位点，并且该过程的准确性可能受到任何方向上的易位率的影响。因此，两个家族的保真度控制可以说依赖于多个基本步骤，每个步骤都对整体保真度有贡献。这些动力学检查点的总和贡献提供了DNA复制和氨基酰化的高观察总体准确性。
DNA polymerases and aminoacyl-tRNA synthetases (ARSs) represent large enzyme families with critical roles in the transformation of genetic information from DNA to RNA to protein. DNA polymerases carry out replication and collaborate in the repair of the genome, while ARSs provide aminoacylated tRNA precursors for protein synthesis. Enzymes of both families face the common challenge of selecting their cognate small molecule substrates from a pool of chemically related molecules, achieving high levels of discrimination with the assistance of proofreading mechanisms. Here, the fidelity preservation mechanisms in these two important systems are reviewed and similar features highlighted. Among the noteworthy features common to both DNA polymerases and ARSs are the use of multidomain architectures that segregate synthetic and proofreading functions into discrete domains; the use of induced fit to enhance binding selectivity; the imposition of fidelity at the level of chemistry; and the use of postchemistry error correction mechanisms to hydrolyze incorrect products in a discrete editing domain. These latter mechanisms further share the common property that error correction involves the translocation of misincorporated products from the synthetic to the editing site and that the accuracy of the process may be influenced by the rates of translocation in either direction. Fidelity control in both families can thus be said to rely on multiple elementary steps, each with its contribution to overall fidelity. The summed contribution of these kinetic checkpoints provides the high observed overall accuracy of DNA replication and aminoacylation.