Preface

The stability of the genome is of crucial importance. Every day, mammalian cells accumulate an estimated 100,000 lesions in their DNA as a result of exposure to reactive oxygen species, chemical deterioration of their bases, and exposure to exogenous agents such as ultraviolet and ionizing radiation. The cells have evolved complex response mechanisms to recognize and repair such injury in order to maintain genomic integrity. With the development of sophisticated molecular techniques, the spectrum of diseases benefitting from the research effort to understand the mechanisms of DNA damage response has grown to include virtually all fields where genotoxic stress plays a role in disease initiation, evolution, and treatment. One of the most important is cancer biology. It is becoming increasingly clear that DNA damage plays an essential role in neurodegeneration. However, the molecular mechanisms of cellular responses to DNA injury and how they influence mutagenesis and cell death remain unclear. This book reviews a number of important DNA repairrelated topics.

The book consists of 31 chapters, divided into six parts. Each chapter is written by one or several experts in the corresponding area. The scope of the book ranges from the DNA damage response and DNA repair mechanisms, to evolutionary aspects of DNA repair, providing a snapshot of current understanding of DNA repair processes. A collection of articles presented by active and laboratory-based investigators gives a clear understanding of the recent advances in the field of DNA repair in various cell types, including bacteria (Davydov et al.; Wang and Maier), germ (Leduc et al.), and neurons (Kruman; Coppedè).

The first part is devoted to various aspects of DNA damage response, focusing on BRCA1 (Boutou et al.; Ratanaphan), BRCA2 (Brown), TopBP1 (Forma et al.), Rad51 (Popova et al.; Boutou et al.), DDB2 (Jones et al.; Chao) and E2F1 (Zhang and Chen; Dagnino et al.) factors, the role of cell cycle machinery in DNA damage response of postmitotic cells (Kruman), the involvement of DNA-repair proteins in centrosome maintenance (Mikio), transcriptional regulatory networks controlling DNA repair pathways (Welch et al.) and on the function of microRNA in DNA damage response (Chen and Chen).

The second part of the book deals with an evolutionary view of DNA repair, focusing on meiosis as an evolutionary adaptation for DNA Repair (Bernstein et al.) and evolution of DNA repair in plants (Vuosku et al.).

The third part discusses the mechanisms of DNA repair, particularly non-homologous end-joining (Kamdar and Matsumoto), homologous recombination (Korolev), global genome nucleotide excision repair (Sugasawa) and the gratuitous repair on undamaged DNA formed by unusual DNA structures generating genomic instability (Pan et al.).

The fourth and fifth parts cover roles of DNA repair gene mutations in carcinogenesis and neurodegeneration (Long et al.; Ankathil; Hansen and Vogel; Coppede), and the role of DNA repair machinery in telomere maintenance (Uchiumi et al., Ueno). In the last part, Dr. Azqueta and colleagues review various applications of the comet assay for quantification of DNA repair capacity, including DNA repair analysis at the level of specific genome regions.

Together, the chapters are a collection of contemporary works on DNA injury and the associated cellular response. While not every topic in the DNA damage response domain could be reviewed in the book, I do believe the authors have done an outstanding job in providing timely and relevant discussions on their respective subjects, allowing the reader to become more familiar with the field. I assume the information contained in this book underscores the significance of DNA repair in the fields of cancer research and neurodegeneration, and the need for continued investigation in this area.

The editor wishis to acknowledge Ms. Alenka Urbancic for her tireless efforts in collecting and organizing all of the manuscripts from our illustrious contributors.

> **Inna Kruman**  Associate Professor Department of Pharmacology and Neuroscience Texas Tech University Health Sciences Center (TTUHSC) Texas USA

**Part 1** 

**DNA Damage Response** 

**1** 

*Georgia* 

**A Recombination Puzzle Solved:** 

*Department of Microbiology, University of Georgia, Athens* 

Ge Wang and Robert J. Maier

**Role for New DNA Repair Systems in** 

*Helicobacter pylori* **Diversity/Persistence** 

*Helicobacter pylori* is a gram-negative, slow-growing, microaerophilic, spiral bacterium. It is one of the most common human gastrointestinal pathogens, infecting almost 50% of the world's population [1]. Peptic ulcer disease is now approached as an infectious disease, and *H. pylori* is responsible for the majority of duodenal and gastric ulcers [2]. There is strong evidence that *H. pylori* infection increases the risk of gastric cancer [3], the second most frequent cause of cancer-related death. *H. pylori* infections are acquired by oral ingestion and is mainly transmitted within families in early childhood [2]. Once colonized, the host can be chronically infected for life, unless *H. pylori* is eradicated by treatment with antibiotics. *H. pylori* is highly adapted to its ecologic niche, the human gastric mucosa. The pathogenesis of *H. pylori* relies on its persistence in surviving a harsh environment, including acidity, peristalsis, and attack by phagocyte cells and their released reactive oxygen species [4]. *H. pylori* has a unique array of features that permit entry into the mucus, attachment to epithelial cells, evasion of the immune response, and as a result, persistent colonization and transmission. Numerous virulence factors in *H. pylori* have been extensively studied, including urease, flagella, BabA adhesin, the vacuolating cytotoxin (VacA), and the cag pathogenicity island (cag-PAI) [5]. In addition to its clinical importance, *H. pylori* has become a model system for persistent host-associated microorganisms [6]. How *H. pylori* can adapt to, and persist in, the human stomach has become a problem of general interest in

*H. pylori* displays exceptional genetic variability and intra-species diversity [7]. Allelic diversity is obvious as almost every unrelated isolate of *H. pylori* has a unique sequence when a sequenced fragment of only several hundred base pairs is compared among strains for either housekeeping or virulence genes [8-10]. Approximately 5% nucleotide divergence is commonly observed at the majority of gene loci between pairs of unrelated *H. pylori* strains [11]. *H. pylori* strains also differ considerably in their gene contents, the genetic macro-diversity. The two sequenced strains 26695 and J99 share only 94% of their genes, whereas approximately 7% of the genes are unique for each strain [12, 13]. Supporting

**1. Introduction** 

**1.1 Helicobacter pylori pathogenesis** 

both microbial physiology and in pathogenesis areas.

**1.2 Genetic diversity of** *H. pylori*
