期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 9, 页码 3310-3315出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0511259103
关键词
thymic lymphoma; aneuploidy; translocations
资金
- NCI NIH HHS [CA109901, P01 CA092625, CA92625, P01 CA109901] Funding Source: Medline
- NIGMS NIH HHS [R01 GM065812, R56 GM065812, GM65812] Funding Source: Medline
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(-/-)/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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据