Preface

During the last few years, many advances in the knowledge of DNA repair mechanisms were made in eukaryotic cells, thanks to innovative technologies in cellular and molecular biology. However, due to the complexity of cellular physiology, the whole mechanism is still under investigation, highlighting different factors that affect DNA repair efficiency in human cells. The role of proteins involved in DNA repair has been widely studied, but the modality and power of extrinsic and intrinsic factors in influencing protein functionality and correct protein-protein interactions represent a research area under constant investigation. Among intrinsic factors affecting DNA repair processes, there is epigenetics, which strongly impacts on gene expression regulation of DNA repair genes and the complex network of DNA-damage response-related genes. The structure and function of the epigenome under physiological and pathological conditions in the presence of DNA damage are an open and rapidly growing research field. Moreover, in mammalian aged cells, accumulated DNA damage is a source of genomic instability if proper repair is not carried out.

The book is divided into four sections with chapters describing different topics connected to DNA repair in human cells. The first section contains the introductory chapter dealing with the subjects of the book. The second section is dedicated to the role of protein-protein interactions during DNA repair in nuclear and mitochondrial compartments. The third section is dedicated to the relationship between the epigenome and DNA repair in normal and cancer cells. The fourth section is about the interconnection between aging and DNA repair. This last section also contains a chapter on the relationship between the angiogenesis of cancer cells and DNA damage repair and a chapter on the DNA repair-enhancing property of glucan.

I acknowledge the authors that contributed to this book and hope that the topics here discussed may suggest readers to explore new avenues and aspects of the interconnection between different DNA lesions and responses essential for the maintenance of nuclear and mitochondrial genome stability.

> **Maddalena Mognato, PhD**  Department of Biology, University of Padova, Italy

**1**

Section 1

Introduction

Section 1 Introduction

**3**

damaging agent.

**Chapter 1**

Challenge

**1. Introduction**

*Maddalena Mognato*

Introductory Chapter: DNA

epigenetics, chromatin structure, mitochondrial function, and aging.

Epigenetics regulate gene function through posttranslational modifications of histones, DNA methylation noncoding RNAs, and when DNA is damaged, epigenetic alterations can occur at sites of lesions. Epigenetic alterations that occur during DNA repair are mostly transient, being the original epigenetic marker restored. However, sometimes, epigenetic alterations can persist after DNA repair as a sort of "scars" [3]. What is the role of such epigenetic markers left after repair? Epigenetic modifications occur either in normal cells or in cancer cells, representing a further element for cancerogenesis in this last case. Numerous studies reported gene expression changes in human cancers and found signature for specific type of tumors. Each cancer has its own genetic and epigenetic profile, which increases the difficulty to comprehend the process of tumorigenicity. In this regard, the response to each tumor to different DNAdamaging agents is related to the characteristics of its genetic and epigenetic landscape. The structure of chromatin around DNA damage changes significantly to promote DNA repair proteins accessibility. During DNA repair, the structure of chromatin is modified as a consequence of new histone incorporation, replacement, and modification. The coordination of DNA repair protein interactions is a critical process which needs to be fully elucidated, also in relation to the specific DNA-

Mitochondria, with their own DNA, are organelles that are on the rise for several reasons, including the repair of their proper DNA, the mtDNA. Mitochondrial DNA is different from the nuclear one, being circular, without histones, and present in multiple copies. The repair of mtDNA relies on the activity of proteins encoded by

Repair in Human Cells - A Daily

The faithful repair of DNA is a challenge that human cells have to fight every day to maintain genomic stability. The type and frequency of DNA lesions are related to both endogenous and exogenous sources of DNA damage. In addition to normal metabolism, which is responsible for a great number of DNA lesions (approximately 70,000 per cell) [1, 2], environmental agents (i.e., ionizing radiation, UV light, and chemicals) contribute to enhance such number. The capacity of cells to faithfully repair their proper DNA is the primary goal to safeguard the genome integrity. To this purpose, eukaryotic cells have evolved accurate repair systems to overcome the different lesions induced by both external and internal sources of DNA damage. A lot of information is now available for most repair systems, and in the last decades, a lot of efforts have been made in the comprehension of the role of DNA repair proteins, in relation to the type of damage and the effectiveness of repair carried out by different complexes. Besides the molecular role of proteins in such pathways, several other important factors can affect the efficiency of DNA repair, including

### **Chapter 1**
