The DDR is triggered by a wide variety of physico-chemical aberrations in the genome. Depending on the source of damage, diverse lesions in the DNA can be induced, including nucleotide alterations (mutation, substitution, deletion and insertion), bulky adducts, single strand breaks (SSBs) and double strand breaks (DSBs) . Genotoxic agents, such as ultraviolet light from the Sun and IR from e.g., cosmic radiation and medical treatments utilizing X-rays or γ-radiation, mainly cause changes or losses of bases (abasic sites), crosslinks formed between two complementary DNA strands, SSBs and DSBs. Such types of DNA damage can occur separately or in conjunction with one another, resulting in complex DNA damage (clustered lesions). Chemical agents used in cancer therapy can also induce a diversity of DNA lesions, such as intrastrand or interstrand crosslinks. Apart from these environmental agents and genotoxic chemicals, DNA aberrations can also arise from physiological processes such as base mismatches introduced during DNA replication  and from the release of reactive oxygen and nitrogen species (ROS/RNS) upon oxidative respiration or through redox-cycling events mediated by heavy metals . Additionally, replication stress resulting from oncogenic signaling may cause genome instability .