Table 1.
Summary of V(D)J recombination and CSR phenotypes associated with major cNHEJ and DDR factors.
| Gene | Type of Mutation | IR sensitivity | Mice | V(D)J recombination | Class switch recombination | Ref. | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chromosomal | Episomal/Plasmid | IgG1 % of Ctrl | Resection | MH at junctions | ||||||||
| SJ (blunt) | CJ (hairpin) | SJ (blunt) | CJ (hairpin) | |||||||||
| non-homologous end-joining | KU70 | Null | ++++ | sick | ↓↓↓ | ↓↓↓ | ↓↓↓ | ↓↓↓ | ~30% | N.D. | ↑ | 45,167,196–198 |
| KU80/86 | Null | ++++ | sick | ↓↓↓ | ↓↓↓ | ↓↓↓ | ↓↓↓ | ~30% | N.D. | ↑ | 43,44,135,167,199,200 | |
| XRCC4 | Null | ++++ | lethal | ↓↓↓ | ↓↓↓ | ↓↓↓ | ↓↓↓ | ~30% | ↑↑ | ↑↑ | 157,201,202 | |
| LIG4 | Null | ++++ | lethal | ↓↓↓ | ↓↓↓ | ↓↓↓ | ↓↓↓ | ~30% | ↑↑ | ↑↑ | 46,159,166,203–206 | |
| XLF | Null | +++ | live | − | − | ↓↓ | ↓↓ | ~50% | N.D. | ↑↑ | 81,83,84,207 | |
| DNA-PKcs | Null | +++ | live | −1 | ↓↓↓ | ↓ | ↓↓↓ | 90% | ↑↑ | ↑↑ | 51,52,103–105,208 | |
| ARTEMIS | Null | ++ | live | − | ↓↓↓ | − | ↓↓↓ | >90% | N.D. | ↑↑ | 53,90,209–213 | |
| DNA-PKcs | KD | ++++ | lethal | ↓↓↓ | ↓↓↓ | ↓↓ | ↓↓↓ | 30% | ↑↑ | ↑↑ | 55,106 | |
| DNA-PKcs | T2609A | ++ | sick | − | − | ↓ | − | >90% | ↑ | ↑↑ | 70,72,73,76,78–80,89,214 | |
| DNA-PKcs | S2056A | + | live | − | − | ↓ | ↓ | 100% | − | − | 76,77,214 | |
| PAXX | Null | + | live | − | − | − | − | 100% | − | − | 132–136,215–217 | |
| MRI/CYREN | Null | + | live | − | − | N.D. | N.D. | ~90% | N.D. | N.D. | 139,140,218 | |
| DNA damage response | ATM | Null | ++++ | live | − | ↓2 | − | − | 50% | ↑ | ↑↑ | 85,123,148,190,219–224 |
| ATM | KD | ++++ | lethal | − | ↓2 | N.D. | N.D. | 50% | N.D. | N.D. | 123,151,152 | |
| ATM | S1987A | −4 | live | − | − | N.D. | N.D. | 100% | N.D. | N.D. | 125,126 | |
| H2AX | Null | +++ | live | − | − | N.D. | N.D. | ~30% | N.D. | ↑↑ | 178,179,190,225–228 | |
| MDC1 | Null | +++ | live | − | − | N.D. | N.D. | ~50% | N.D. | N.D. | 94,143,145,229 | |
| 53BP1 | Null | ++ | live | − | − | N.D. | N.D. | 5% | ↑↑ | ↑↑ | 146,188–190,230,231 | |
| RIF1 | Null | +++ | lethal | − | − | N.D. | N.D. | 10% | ↑↑ | ↑↑. | 187,188,190,232,233 | |
| REV7 | Null | +++ | sick | − | − | N.D. | N.D. | 10% | ↑↑ | N.D. | 183,234–236 | |
| SHLD1/2/3 | Null | ++ | N.D. | − | − | N.D. | N.D. | 10% | ↑↑ | N.D. | 183,185,186 | |
| PTIP | Null | ++ | lethal | N.D. | N.D. | N.D. | N.D. | ~50% | N.D. | N.D. | 181,237–241 | |
| Combinations | XLF&ATM | Null | ++++ | live | ↓↓↓ | ↓↓↓ | ↓↓ | ↓↓ | 30% | N.D. | N.D. | 85 |
| XLF&H2AX | Null | ++++ | lethal | ↓↓↓ | ↓↓↓ | N.D. | N.D. | N.D. | N.D. | N.D. | 85 | |
| XLF&MDC1 | Null | ++++ | lethal | ↓↓ | ↓↓ | N.D. | N.D. | N.D. | N.D. | N.D. | 94 | |
| XLF&53BP1 | Null | ++++ | live | ↓↓↓ | ↓↓↓ | N.D. | N.D. | N.D. | N.D. | N.D. | 91,92 | |
| XLF&ART | Null | ++++ | live | − | ↓↓↓ | N.D. | ↓↓↓ | N.D. | N.D. | N.D. | 90 | |
| XLF&DNA-PKcs | Null | ++++ | sick | ↓↓ | ↓↓↓ | N.D. | ↓↓↓ | ~50% | N.D. | N.D. | 90 | |
| XLF&PAXX | Null | ++++ | lethal | ↓↓↓ | ↓↓↓ | N.D. | N.D. | N.D. | N.D. | N.D. | 134–136,242,243 | |
| XLF&MRI | Null | ++++ | lethal | ↓↓↓ | ↓↓↓ | N.D. | N.D. | N.D. | N.D. | N.D. | 139 | |
| DNA-PKcs&ATM | Null | ++++ | lethal | ↓↓↓ | ↓↓↓ | ↓↓ | ↓↓↓ | ~20% | N.D. | N.D.3 | 70,87,88,93,244,245 | |
| DNA-PKcs&ATM | T2609A/Null | N.D. | N.D. | ↓↓↓ | ↓↓↓ | ↓ | ↓ | N.D. | N.D. | N.D. | 65,76,80 | |
| DNA-PKcs&ATM | S2056A/Null | N.D. | Live* | − | − | ↓ | ↓ | 50% | N.D. | N.D. | 65,76,77 | |
N.D., not determined; −, no change;
1
reduced fidelity;
2
Hybrid join formation;
3
increased insertion;
4
IR sensitive in human cells;
*
unpublished data.