| First Author | Zan H | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14244 | PubMed ID | 28176781 |
| Mgi Jnum | J:244154 | Mgi Id | MGI:5912933 |
| Doi | 10.1038/ncomms14244 | Citation | Zan H, et al. (2017) Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination. Nat Commun 8:14244 |
| abstractText | Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S-S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase theta to CSR. Compared with their Rad52+/+ counterparts, which display normal CSR, Rad52-/- B cells show increased CSR, fewer intra-Smu region recombinations, no/minimal microhomologies in S-S junctions, decreased c-Myc/IgH translocations and increased Ku70/Ku86 recruitment to S-region DSB ends. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends. It also facilitates a Ku-independent DSB repair, which favours intra-S region recombination and mediates, particularly in Ku absence, inter-S-S recombination, as emphasized by the significantly greater CSR reduction in Rad52-/- versus Rad52+/+ B cells on Ku86 knockdown. |
