Accuracy in Molecular Processes: Its Control and Relevance to Living System

Molecular biology proceeds at unremitting pace to unfold new secrets of the living world. Biology, long regarded as an inexact companion to physics and chemistry, has undergone transformation. Now, chemical and physical principles are tools in understanding highly complex biomolecular processes, whose origin lies in a history of chance, constraint and natural selection. The accuracy of these processes, often remarkably high, is crucial to their self- perpetuation, both individually and collectively, as ingredients of the organism as a whole. In this book are presented thirteen chapters which deal with various facets of the accuracy problem. Subjects covered include: the specificity of enzymes; the fidelity of synthesis of proteins; the replication and repair of DNA: general schemes for the enhancement of biological accuracy; selection for an optimal balance between the costs and benefits of accuracy; and the possible relevance of molecular mistakes to the process of ageing. The viewpoints are distinct, yet complementary, and the book as a whole offers to researchers and students the first comprehensive account of this growing field.

Table of Contents:
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.