Morales, Julio C.Franco, SoniaMurphy, Michael M.Bassing, Craig H.Mills, Kevin D.Adams, Melissa M.Walsh, Nicole C.Manis, John P.Rassidakis, George Z.Alt, Frederick W.Carpenter, Phillip B.2019-10-052006Morales, J. C., S. Franco, M. M. Murphy, C. H. Bassing, K. D. Mills, M. M. Adams, N. C. Walsh, et al. 2006. “53BP1 and p53 Synergize to Suppress Genomic Instability and Lymphomagenesis.” Proceedings of the National Academy of Sciences 103 (9): 3310–15. https://doi.org/10.1073/pnas.0511259103.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483431p53-binding protein 1 (53BP1) participates in the cellular response to DNA double-stranded breaks where it associates with various DNA repair/cell cycle factors including the H2AX histone variant. Mice deficient for 53BP1 (53BP1(-/-)) are sensitive to ionizing radiation and immunodeficient because of impaired Ig heavy chain class switch recombination. Here we show that, as compared with p53(-/-) mice, 53BP1(-/-)/p53(-/-) animals more rapidly develop tumors, including T cell lymphomas and, at lower frequency, B lineage lymphomas, sarcomas, and teratomas. In addition, T cells from animals deficient for both 53BP1 and p53 (53BP1(-/-)/1p53(-/-)) display elevated levels of genomic instability relative to T cells deficient for either 53BP1 or p53 alone. In contrast to p53(-/-) T cell lymphomas, which routinely display aneuploidy but not translocations, 53BP1(-/-)1p53(-/-) thymic lymphomas fall into two distinct cytogenetic categories, with many harboring clonal translocations (40%) and the remainder showing aneuploidy (60%). We propose that 53BP1, in the context of p53 deficiency, suppresses T cell lymphomagenesis through its roles in both cell-cycle checkpoints and double-stranded break repair.en-USJournal Article2019-10-0510.1073/pnas.0511259103