| First Author | Marton T | Year | 2025 |
| Journal | Nat Commun | Volume | 16 |
| Issue | 1 | Pages | 10536 |
| PubMed ID | 41298353 | Mgi Jnum | J:375903 |
| Mgi Id | MGI:8267441 | Doi | 10.1038/s41467-025-65555-9 |
| Citation | Marton T, et al. (2025) Polymerase theta repairs persistent G1-induced DNA breaks in S-phase during class switch recombination. Nat Commun 16(1):10536 |
| abstractText | Non-homologous end joining (NHEJ) is the primary pathway for repairing G1 phase-induced DNA double-strand breaks (DSBs) during immunoglobulin heavy chain (Igh) class switch recombination (CSR) in B lymphocytes. In B cells lacking NHEJ (XRCC4) or DSB end protection (SHLD1), end joining during CSR proceeds through an alternative end-joining pathway. Polymerase theta (Pol theta) is widely regarded as a mediator of this pathway, essential for repairing replication-associated DSBs during mitosis when homologous recombination is unavailable. In this study, we examined CSR in primary B cells lacking XRCC4, SHLD1, and/or Pol theta, revealing two repair pathways: Pol theta-independent productive switching and Pol theta-dependent unproductive switching characterized by end resection, inversion and microhomology. Furthermore, we show that Pol theta-mediated repair under NHEJ-deficiency coincides with G1-to-S phase transition and occurs independently of RHINO and PLK1. Thus, in the absence of NHEJ, Pol theta repairs persistent G1-phase DSBs during S-phase rather than mitosis. |
