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Molecular Biology Inteligence Unit - DNA and RNA Modification Enzymes: Structure, Mechanism, Function, and Evolution

Description: Modified deoxy- and ribonucleosides, distinct from the canonical nucleosides adenosine, guanosine, cytosine and uridine or thymidine, are found in DNA and RNAs of all living organisms, as well as of viruses, mitochondria and chloroplasts. In DNA, chemical alteration of a base or a phosphate occurs by pre-replicative or post-replicative enzymatic processes, while in RNAs, chemical alteration of a base or a ribose always occurs aft er RNA synthesis, at the polymer level. DNA and RNA editing, that is the replacement of a canonical base by another at the polymer level, also exists in eukaryotic cells, certain archaea, in mitochondria and chloroplasts.

The variety of biochemical processes allowing such nucleic acids modifi cation and editing are astonishing. Th ey infl uence the maturation, folding and stabilization of RNAs and allow an accurate, effi cient and regulated translation process. In DNA, they allow genetic imprinting, immunoglobulin class switch recombination, somatic hypermutation, self-defence against viruses and probably many other functions that have still to be discovered. Th e challenge is to understand how and why these intriguing, very diversified types of ‘fine-tuning’ the structure and functions of nucleic acids by so-called ‘minor nucleosides’ have emerged since the fi rst living cells appeared on earth some millions of years ago.

This volume is a timely and comprehensive description of the many facets of DNA and RNA modifi cation-editing processes and to some extent repair mechanisms. Each chapter offers fundamental principles as well as up to date information on recent advances in the fi eld (up to the end of 2008). Th ey conclude with a short ‘conclusion and future prospect’ section and an exhaustive list of 35 to up to 257 references (in average 87). Contributors are geneticists, structural enzymologists and molecular biologists working at the forefront of this exciting, fast-moving and diverse field. Th is book will be a major interest to PhD students and University teachers alike. It will also serve as an invaluable reference tool for new researchers in the field, as well as for specialists of RNA modification enzymes generally not well informed about what is going on in similar processes acting on DNA and vice-versa for specialists of the DNA modification-editing and repair processes usually not much acquainted with what is going on in the RNA maturation field.

The book is comprised of 41 chapters. Th e common links between them are mainly the enzymatic aspects of the different modification-editing and repair machineries: structural, mechanistic, functional and evolutionary aspects. It starts with two general and historical overviews of the discovery of modified nucleosides in DNA and RNA and corresponding modification-editing enzymes. Th en follows 11 chapters on DNA modification and editing (mechanistic and functional aspects). Two additional chapters cover problems related to DNA/RNA repair and base editing by C-to-U deaminases, followed by three chapters on RNA editing by C-to-U and A-to-I type of deamination. Discussions about the interplay between DNA and RNA modifi cations and the emergence of DNA are covered in two independent chapters, followed by 20 chapters on diff erent but complementary aspects of RNA modifi cation enzymes and their cellular implications. Th e last chapter concerns the description of the present state-of-the art for incorporating modifi ed nucleosides by in vitro chemical synthesis. At the end of the book, six appendices give useful details on modified nucleosides, modification-editing enzymes and nucleosides analogs. Th is information is usually diffi cult to obtain from current scientific literature.

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