DNA polymerases and aminoacyl-tRNA synthetases: shared mechanisms for ensuring the fidelity of gene expression.
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.
Francklyn
Christopher S
CS
Department of Biochemistry, Department of Microbiology, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA. Christopher.Francklyn@uvm.edu
D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000378:metabolism*; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D014176:Protein Biosynthesis
D004259:DNA-Directed DNA Polymerase; D000604:Amino Acyl-tRNA Synthetases