**Abstract**

Radiation is one of the causative agents for the induction of DNA damage in biological systems. There is various possibility of radiation exposure that might be natural, man-made, intentional, or non-intentional. Published literature indicates that radiation mediated cell death is primarily due to DNA damage that could be a single-strand break, double-strand breaks, base modification, DNA protein cross-links. The double-strand breaks are lethal damage due to the breakage of both strands of DNA. Mammalian cells are equipped with strong DNA repair pathways that cover all types of DNA damage. One of the predominant pathways that operate DNA repair is a non-homologous end-joining pathway (NHEJ) that has various integrated molecules that sense, detect, mediate, and repair the double-strand breaks. Even after a well-coordinated mechanism, there is a strong possibility of mutation due to the flexible nature in joining the DNA strands. There are alternatives to NHEJ pathways that can repair DNA damage. These pathways are alternative NHEJ pathways and single-strand annealing pathways that also displayed a role in DNA repair. These pathways are not studied extensively, and many reports are showing the relevance of these pathways in human diseases. The chapter will very briefly cover the radiation, DNA repair, and Alternative repair pathways in the mammalian system. The chapter will help the readers to understand the basic and applied knowledge of radiation mediated DNA damage and its repair in the context of extensively studied NHEJ pathways and unexplored alternative NHEJ pathways.

**Keywords:** Radiation, DNA damage, DNA repair, NHEJ, Alternative NHEJ

## **1. Introduction**

Radiation is a natural part of our surroundings. Humans get exposure to natural radiation such as cosmic rays and radioactivity from earth and food. The diversified use of radiation in several technological procedures like power generation, sterilization of food products, industrial activities, therapeutics (radiotherapy), diagnosis,

nuclear weapon development etc., has increased the risk of exposure. Inadvertent accidents from nuclear power plant installations, nuclear weapon testing and illegal use of radioactive material in dirty bomb have raised an international concern for radiation safety [1–3].

Radiation therapy is the most common and deliberate exposure of high energy rays to living organisms. This exposure is mainly therapeutic for treatment of cancer but since there is no clear demarcation to protect the adjacent noncancerous cells leads to disastrous effect. The immediate exposure of high energy beam of radiation leads to destruction of cancerous cells. Whereas the adjacent normal cells are however exposed to these rays suffer adverse effects. It indirectly generates reactive oxygen species (ROS) inside the cellular system through hydrolysis of water. ROS directly targets cellular DNA and affect the cell survival by damaging macromolecules like lipid, proteins and carbohydrate. The damage induction in DNA molecules could be of various types like double strand break, single strand break, dimer formation, alteration of bases etc. Mammalian cells are equipped with very efficient DNA repair mechanism to handle these different damages [4]. Moreover among all, double strand breaks are known to be lethal damage for the cells. There are mainly two repair mechanisms that operate for repair of double strand breaks. These are 1) Homologous repair pathway (HR) 2) Non homologous end joining pathway (NHEJ). The basis on which cell decides to choose one of the two available pathways is simply on cell cycle phase, its type and damage threshold [5]. There are also exists third repair pathway i.e. Alternative non homologous end joining pathway (A-NHEJ) it is much slower than the above mentioned pathway. It comes into play when above mentioned pathway fail to repair the damage thus acting as a backup pathway. The presence of this alternative pathway has not been studied extensively but it has been speculated for its role in combinational cancer therapeutics. In this chapter, we have briefly described the various kind of DNA damage generated by radiation and role of DNA repair pathways specially NHEJ and A-NHEJ in handling the repair and their applications in progression of disease [6].

Radiation, which has particles with enough energy to rip electron from atoms or molecules is known as ionizing radiation. Radiation is the emission and propagation of energy in the form of rays or waves. The term radiation comes after the discovery of X-ray in 1895 by Wilhelm Conrad Roentgen. Henri Becquerel and Marie Curie have made significant contributions in studying the effect and application of radiation in various fields. Excitation and ionization properties are common responsible factor for radiation emitted by any radioisotopes. It has two major types: ionizing and non-ionizing radiation [6, 7].

#### **1.1 Non-ionizing radiation**

It does not carry enough energy to remove electrons from an atom or molecule. Because of their low energy, non-ionizing radiation poses a lower risk than ionizing radiation. Visible light, near ultra violet, infrared, microwave and radio waves are examples of non-ionizing radiation [5].

#### **1.2 Ionizing radiation**

Ionizing radiation (IR), as the name indicates carry sufficient energy to remove electrons from atoms or molecules. It can be in particulate or electromagnetic form. The particulate forms consist electrons, protons, neutrons, α-particles etc. and the electromagnetic form includes as cosmic rays, X-rays, gamma rays etc. [5]. Ionizing radiation exposure may cause tissue injuries to the biological system

**101**

**Figure 1.**

*Various type of DNA damage induce by radiation.*

*Recent Perspectives in Radiation-Mediated DNA Damage and Repair: Role of NHEJ…*

via biochemical, cellular and molecular targets leading to cellular and molecular damages such as oxidative damage to DNA, lipids and proteins as shown in **Figure 1**

An alpha ray consists of two protons and two neutrons. These rays have a strong nuclear force and have the ability to bind to the nucleus of any atom. Due to their charge and mass, alpha particles interact strongly with matter and only travel a few centimeters in air. Alpha particles are unable to penetrate the outer layer of dead skin cells but are capable of causing serious cell damage if an alpha emitting sub-

Beta particles are high-speed electron or positron emitted from the radioactive decay of an atomic nucleus such as potassium-40 during beta decay. These particles

*DOI: http://dx.doi.org/10.5772/intechopen.96374*

**1.3 Types of ionizing radiation**

stance is ingested in food or air [5].

*1.3.1 Alpha particles*

*1.3.2 Beta particles*

which may further lead to systemic damage [6, 8].

*Recent Perspectives in Radiation-Mediated DNA Damage and Repair: Role of NHEJ… DOI: http://dx.doi.org/10.5772/intechopen.96374*

via biochemical, cellular and molecular targets leading to cellular and molecular damages such as oxidative damage to DNA, lipids and proteins as shown in **Figure 1** which may further lead to systemic damage [6, 8].
