p53-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-/-/p53 -/-) 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-/-/p53-/- 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.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - Feb 28 2006|
- Thymic lymphoma
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