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Working model for joining of various types of DNA DSBs. First, DSB recognition by Ku70/80 is fast and reversible. Subsequently, XRCC4/ligase IV can be attracted, forming a reversible complex. Alternatively, DNA-PKCS and XRCC4/ligase IV can both be recruited and form a more stable complex. We hypothesize that the joining reaction of simple DSBs can be accomplished via either of these two intermediates, whereas complex DSBs can be joined only via the right branch.
