| First Author | Li G | Year | 2008 |
| Journal | Mol Cell | Volume | 31 |
| Issue | 5 | Pages | 631-40 |
| PubMed ID | 18775323 | Mgi Jnum | J:138774 |
| Mgi Id | MGI:3806383 | Doi | 10.1016/j.molcel.2008.07.017 |
| Citation | Li G, et al. (2008) Lymphocyte-specific compensation for XLF/cernunnos end-joining functions in V(D)J recombination. Mol Cell 31(5):631-40 |
| abstractText | Mutations in XLF/Cernunnos (XLF) cause lymphocytopenia in humans, and various studies suggest an XLF role in classical nonhomologous end joining (C-NHEJ). We now find that XLF-deficient mouse embryonic fibroblasts are ionizing radiation (IR) sensitive and severely impaired for ability to support V(D)J recombination. Yet mature lymphocyte numbers in XLF-deficient mice are only modestly decreased. Moreover, XLF-deficient pro-B lines, while IR-sensitive, perform V(D)J recombination at nearly wild-type levels. Correspondingly, XLF/p53-double-deficient mice are not markedly prone to the pro-B lymphomas that occur in previously characterized C-NHEJ/p53-deficient mice; however, like other C-NHEJ/p53-deficient mice, they still develop medulloblastomas. Despite nearly normal V(D)J recombination in developing B cells, XLF-deficient mature B cells are moderately defective for immunoglobulin heavy-chain class switch recombination. Together, our results implicate XLF as a C-NHEJ factor but also indicate that developing mouse lymphocytes harbor cell-type-specific factors/pathways that compensate for the absence of XLF function during V(D)J recombination. |
