Table 1. NHEJ proteins and their proposed roles.
Three classes of proteins comprise the NHEJ machinery: core factors, whose loss results in severe NHEJ defects; accessory factors, which interact with core factors but whose loss results in mild defects; and end processing enzymes, which chemically modify damaged DNA ends to prepare them for ligation.
| NHEJ PROTEIN | PROPOSED ROLE(S) IN NHEJ |
|---|---|
| Core factors | |
| Ku70/80 | Initial DSB sensor and interaction hub (11), 5′dRP/AP lyase (175) |
| DNA-PKcs | Kinase activity (13), end synapsis (53, 56, 69), and molecular “gate” (13) |
| LIG4 | Catalytic role in ligation (19), structural role in synapsis (53, 56, 58, 72) |
| XRCC4 | Constitutive LIG4 interactor (19), XLF interactor for synapsis (53, 55, 56, 58, 77) |
| XLF | XRCC4 interactor for synapsis (53, 55, 56, 58, 77, 80) |
| Accessory factors | |
| PAXX | Synapsis (56), redundant roles with XLF (95, 96) |
| APLF | Scaffolding factor (98) |
| WRN | Helicase and exonuclease (99), role in repair pathway choice (101) |
| MRI/CYREN | Cell cycle regulator of NHEJ (102, 103) |
| End processing enzymes | |
| Damage correction | |
| PNKP | 5′ kinase, 3′ phosphatase (130) |
| TDP1 | Removal of TOP1 (136) and other 3′ adducts (138) |
| TDP2 | Removal of TOP2 5′ adducts (137) |
| Aprataxin | Removal of 5′ adenylate (132) |
| Polymerases | |
| Pol λ | Templated synthesis, paired primer terminus (127) |
| Pol μ | Templated synthesis, unpaired primer terminus (127) |
| TdT | Untemplated synthesis during V(D)J recombination (35) |
| Nucleases | |
| Artemis | V(D)J hairpin opening (32), processing of some IR DSBs (114) |
| SETMAR/Metnase | ssDNA endonuclease (117) |