The study of complex DNA damage in terms of in situ detection involves the concept of DNA repair colocalization (DNA repair centers) as previously introduced for DSBs  and non-DSB damage . The term “colocalization” actually refers to the spatiotemporal coexistence of two or more proteins of different type. The detection of complex DNA lesions consisting of a variety of DSBs and OCDLs is made possible through the visualization of proteins participating in a distinct DNA repair mechanism, e.g. one protein participating in the base excision repair (BER) processing base lesions and another one participating in the homologous recombination (HR) or the non-homologous end joining (NHEJ) for the repair of DSBs. As shown in Figure 2, upon the induction of a cluster of DNA lesions, several DNA repair pathways and proteins will be involved. For short-patch BER, a DNA glycosylase will arrive, excise the damaged base and the repair will be completed presumably by the human AP endonuclease 1 (APE1), a polymerase and ligase III to seal the broken ends. In the nearby DSB area (within a few bp apart), the Ku heterodimer (Ku70/80) initiates NHEJ by binding to the free DNA ends and engaging other NHEJ factors such as DNA-dependent protein kinase (DNA-PK), XRCC4, and DNA Ligase IV to the site of the break. DNA-PK becomes activated upon DNA binding, and phosphorylates a number of substrates including p53, Ku, and DNA Ligase IV cofactor XRCC4. Phosphorylation of these factors is believed to further facilitate the processing of the break. Finally, in order for ligation to occur, a partial processing of the ends by nucleases Artemis, MRE11/Rad50/NBS1 complex and FEN-1 is taking place.