Accuracy in Molecular Processes

1 An introduction to the problem of accuracy.- 1.1 Setting the scene.- 1.2 Some preliminary concepts.- 1.3 The accuracy of enzymes.- 1.4 The role of kinetics in accuracy.- 1.5 Molecular accuracy in evolution.- 1.6 Accuracy in other information systems.- References.- 2 Errors and the integrity of genetic information transfer.- 2.1 Introduction.- 2.2 Theory.- 2.3 Experimental observations on protein errors and error feedback.- 2.4 Errors in the control of transcription and in the timing of cell cycle events.- 2.5 Conclusions.- References.- 3 The specificity of enzyme-substrate interactions.- 3.1 Introduction.- 3.2 Kinetics and thermodynamics.- 3.3 Rates of reaction and accuracy.- 3.4 Discrimination through binding.- 3.5 Molecular mechanisms.- 3.6 Molecular fit.- References.- 4 The charging of tRNA.- 4.1 Introduction.- 4.2 The basic problem in amino acid selection.- 4.3 The basic kinetic equations of specificity.- 4.4 The discovery of editing during amino acid selection.- 4.5 The editing reaction pathway: hydrolysis of mischarged tRNA versus hydrolysis of misactivated amino acid.- 4.6 The double-sieve editing mechanism.- 4.7 The economics of editing.- 4.8 The relative importance of the pre-transfer and post- transfer pathways.- 4.9 Chemical reaction mechanisms of editing.- 4.10 Aminoacyl-tRNA synthetases not requiring editing mechanisms.- References.- 5 The accuracy of mRNA-tRNA recognition.- 5.1 Introduction.- 5.2 How specific is the process of translation?.- 5.3 Decoding of the third codon base.- 5.4 Tuning the codon-anticodon interaction.- 5.5 Concluding remarks.- References.- 6 The secret life of the ribosome.- 6.1 Introduction.- 6.2 Missense error frequencies.- 6.3 Bioenergetics of translation.- 6.4 Translation in vitro.- 6.5 Curious consequences of proofreading.- 6.6 Error coupling.- 6.7 Suppression of frameshift mutations.- 6.8 Modalities of error coupling.- 6.9 Concluding remarks.- References.- 7 The accuracy of RNA synthesis.- 7.1 Introduction.- 7.2 Accuracy during RNA polymerization.- 7.3 Accuracy during initiation of RNA synthesis.- 7.4 Accuracy during termination of RNA synthesis.- 7.5 Accuracy during mRNA splicing.- 7.6 Accuracy during maturation of the 3? terminus of an mRNA.- 7.7 Conclusions.- References.- 8 DNA replication fidelity and base mispairing mutagenesis.- 8.1 Introduction.- 8.2 Km discrimination model.- 8.3 Evidence in support of a Km discrimination model for fidelity.- 8.4 Further predictive potential of the Km model.- 8.5 Concluding remarks.- References.- 9 Stability and change through DNA repair.- 9.1 Introduction.- 9.2 Types of DNA damage and cellular responses.- 9.3 Removal repair.- 9.4 Recombinational repair.- 9.5 Replicative repair and induced mutagenesis.- 9.6 DNA damage and epigenetic change.- 9.7 Evolution of indirect mutagenesis.- 9.8 DNA repair effects in multicellular organisms.- References.- 10 Kinetic and probabilistic thinking in accuracy.- 10.1 Introduction.- 10.2 Hidden principles behind the kinetic formalism.- 10.3 The sequestration effect.- 10.4 Kinetic modulation.- 10.5 Kinetic amplification.- 10.6 Recipes for calculation.- 10.7 Outlook.- References.- 11 Kinetic costs of accuracy in translation.- 11.1 Introduction.- 11.2 Kinetic proofreading revisited.- 11.3 Displacements in enzymic selections.- 11.4 Displacements in kinetic proofreading.- 11.5 Kinetic proofreading in translation.- 11.6 Efficiency of biochemical pathways.- 11.7 Low cost translations.- 11.8 Optimal accuracy in translation.- 11.9 Conclusions.- References.- 12 Selection for optimal accuracy and the evolution of ageing.- 12.1 Introduction.- 12.2 Evolution of accuracy in primitive organisms.- 12.3 Evolution of translational accuracy.- 12.4 The maintenance of the integrity of DNA.- 12.5 Balancing the costs and benefits of accuracy.- 12.6 Optimal accuracy of translation in reproductive and somatic cells.- 12.7 Evolution of ageing and longevity.- 12.8 Predictions and conclusions.- References.- 13 Diversity and accuracy in molecular evolution: sketches past, present and future.- 13.1 Sketch I.- 13.2 Sketch II.- 13.3 Sketch III.- 13.4 Sketch IV.- 13.5 Sketch V.- 13.6 Sketch VI.- 13.7 Sketch VII.- 13.7 Sketch VIII.- References.