Oxidative DNA Damage in Neurons: Implication of Ku in Neuronal Homeostasis and Survival

Figure 1

ROS can generate double-strand breaks with heterogeneous incompatible DNA ends. Following DSB formation, Ku70 and Ku86 form the heterodimer Ku, which can bind directly the two broken DNA termini. Ku, likely changing conformation once it slides onto the DNA end, recruits DNA-PKcs and Artemis to form the DNA-PK complex, which brings the two DNA ends close together and protects them from excessive degradation. DNA-PK phosphorylates itself and also mediates a regulatory phosphorylation of other NHEJ components, such as Artemis. Subsequently, the DNA polymerases (including the pol X polymerases, pol μ and λ) synthetize each DNA segment necessary for the repair. Finally, the DNA-PK complex recruits the LIG4-XRCC4-XLF complex in order to perform the ligation of the DNA termini, after which the DNA-repair factors dissociate.