Review Article

Phosphorylation: The Molecular Switch of Double-Strand Break Repair

Figure 1

NHEJ model. After a DSB has occurred due to an exogenous or endogenous DNA damaging agent, the NHEJ repair process commences. In step 1, the Ku70/80 heterodimer recognizes and binds the DSB, which induces inward translocation of Ku and recruits DNA-PKcs to the ends of the DSB to form DNA-PK. In step 2, depending on the type and complexity of the DSB break, the DNA ends are processed by different processing factors such as, Artemis, PNKP, DNA polymerases, or the MRN complex (MRE11/RAD50/NBSI). Also, DNA-PKcs autophosphorylate in this second step and will then dissociate from the DSBs. In the final step, XLF stimulates the XRCC4/DNA ligase IV complex to ligate the DNA ends to repair the DSB.
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