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. Author manuscript; available in PMC: 2021 Nov 1.
Published in final edited form as: Nature. 2021 Apr 14;593(7858):294–298. doi: 10.1038/s41586-021-03458-7

Figure 4, Structural transition from the LR to the SR synaptic complex.

Figure 4,

a, Superimposition of the LR and SR complexes shown in front (left) and top (right) views. XLF homodimer is used for aligning the two conformers. DNA-PKcs and LigIV catalytic domains are hidden for clarity. The transition from the LR to the SR synaptic state indicates potential conformational changes induced by dissociation of DNA-PKcs and association of the LigIV catalytic domain. b, Model of structural transitions during NHEJ. After DSB detection by Ku70/80, DNA-PKcs is recruited to form a DNA-PK complex by inward translocation on DNA (1). A LigIV-XRCC4-XLF-XRCC4-LigIV scaffold assembles the two DNA-PK complexes into the LR complex, positioning the major auto-phosphorylation clusters near the kinase active centers in a trans manner (2). Upon auto-phosphorylation and dissociation of DNA-PKcs, the complex transitions into the SR complex, allowing the recognition and sealing of one nick by one LigIV catalytic domain (3). The complex next undergoes a conformational change and possibly DNA translocation to allow the recognition and sealing of the other nick by the second LigIV catalytic domain from the opposite side (4). The ligase factors then dissociate, and the DSB is repaired (5).