Mechanisms of Genome Protection and Repair

This volume is about DNA damage and repair. It covers recent advances in several important research areas of this rapidly expanding field, and does so at several levels, from individual molecules to organisms. The topics include mechanisms of damage recognition by DNA repair enzymes, chromatin response to DNA damage, special ways of mutagenesis, biomarkers of genotoxicity, and the integrated organism response to genotoxic and other kinds of stress.The book starts with two chapters about structural and mechanistic features of protein-DNA interactions that ensure fast and reliable discrimination between targets - be it DNA modifications or specific sequences - and non-targets. Examples of particular proteins and their function in repair regulation, translesion synthesis and chromatin remodeling are discussed in the following three chapters. Next, more attention is given to the mutagenic consequences of failed or aberrant DNA repair, particularly in mitochondria and in runs of trinucleotide repeats. Moving to a human health-oriented view, the book presents data on two kinds of lesions, the widely found 8-oxoguanine and the dietary genotoxic adducts with aristolochic acids, as biomarkers of general oxidative stress and specific exposure, respectively. Two final chapters are devoted to the interplay of multiple factors, including genotoxic stress, in the complex phenotypes in humans (amyotrophic lateral sclerosis ) and plants (abiotic stress response).

This volume will be of significant interest for scientists working in the field of DNA repair as well as for the general biochemistry and molecular biology audience.

Autorentext

Dmitriy Zharkov is the head of the Novosibirsk State University laboratory of protein engineering. He is a leading specialist in the field of fundamental mechanisms of DNA damage, DNA reparation and cell response to genotoxic stress. He has discovered several ferments of human reparation, defined special structures of some DNA-glycosylases and developed the theory of substrate specificity of ferments that recognize nucleic acids as dynamic multi-stage process.

Klappentext

DNA is under constant challenge from environmental and endogenous metabolic assaults. Several layers of defence and repair systems allow cells to maintain stable genomes; in humans, dysfunction of these systems leads to cancer, neurodegeneration, and other pathologies. At the same time, recently it had emerged that targeted and regulated DNA damage and repair is a mechanism underlying several important cellular processes such as epigenetic demethylation and immunoglobulin gene diversification. The present collection of papers is aimed to cover new developments in the area of protective and regulatory mechanisms associated with DNA damage. The mechanisms ruling the recognition of damaged nucleotides against the vast background of normal ones are reviewed. The role of extended non-catalytic domains that are often found in eukaryotic DNA repair proteins in contrast to their downsized, catalytic-only bacterial counterparts is discussed. Among the proposed subjects are the regulatory functions of bulky covalent modifications such as poly(ADP)ribosylation and ubiquitylation in DNA damage response, especially in the context of chromatin remodelling. As opposed to DNA repair, damage tolerance allows cells to replicate with lesions in the genome; the enzymes responsible are also covered. Finally, we present examples of modern multilevel understanding of the cell function and malfunction in the wake of genotoxic assaults such as oxidative stress, abiotic environmental stress, and DNA-damaging plant toxins.

Inhalt

Preface

Kinetic Milestones of Damage Recognition by DNA Glycosylases of the Helix-Hairpin-Helix Structural Superfamily

Protein Engineering of DNA-Dependent Enzymes

A Multifunctional Protein PolDIP2 in DNA Translesion Synthesis

Impact of PARP1, PARP2 and PARP3 on the Base Excision Repair of Nucleosomal DNA

Base Excision Repair in Chromatin and the Requirement for Chromatin Remodelling

DNA Repair and Mutagenesis in Vertebrate Mitochondria: Evidence for Asymmetric DNA Strand Inheritance Mystery of Expansion: DNA Metabolism and Unstable Repeats

The Detection of 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine in Circulating Cell-Free DNA: A Step Towards Longitudinal Monitoring of Health

Biotransformation and Toxicities of Aristolochic Acids

Mechanisms of Sugar Beet Response to Biotic and Abiotic Stresses

Studying ALS: Current Approaches, Effect on Potential Treatment Strategy