期刊
CANCER LETTERS
卷 501, 期 -, 页码 43-54出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.12.033
关键词
53BP1; Tumor suppressor; DNA damage repair; Cancer-associated mutations
类别
资金
- National Natural Science Foundation of China [32071277, 31670812, 82002594]
- grant for Returned Overseas Chinese Scholars of Hebei Province [CY201602, C20200303]
- Natural Science Foundation of Hebei province [C2018201171]
- National Foundation of Hebei Educational committee [ZD2020183]
- Ministry of Education ChunHui Project [23]
- Outstanding Youth Science Foundation of Hebei Province [H2020201017]
- High-level Talents Research Start-up Project of Hebei University [521000981352]
The study examined mutations in the TP53 binding protein 1 (53BP1) gene in various human cancers, revealing that these mutations may disrupt the DNA damage repair function of 53BP1 and impact genomic stability.
TP53 binding protein 1 (53BP1) plays an important role in DNA damage repair and maintaining genomic stability. However, the mutations of 53BP1 in human cancers have not been systematically examined. Here, we have analyzed 541 somatic mutations of 53BP1 across 34 types of human cancer from databases of The Cancer Genome Atlas, International Cancer Genome Consortium and Catalogue of Somatic Mutations in Cancer. Among these cancer-associated 53BP1 mutations, truncation mutations disrupt the nuclear localization of 53BP1 thus abolish its biological functions in DNA damage repair. Moreover, with biochemical analyses and structural modeling, we have examined the detailed molecular mechanism by which missense mutations in the key domains causes the DNA damage repair defects. Taken together, our results reveal the functional defects of a set of cancer-associated 53BP1 mutations.
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