Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture
文献类型：期刊论文
| 作者 | Ding, Liang-Hao2; Story, Michael D.2; Minna, John D.3; Shay, Jerry W.4; Chen, David J.2; Asaithamby, Aroumougame2; Hu, Burong1 ; Delgado, Oliver4
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| 刊名 | NUCLEIC ACIDS RESEARCH
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| 出版日期 | 2011-07-01 |
| 卷号 | 39页码:5474-5488 |
| ISSN号 | 0305-1048 |
| DOI | 10.1093/nar/gkr149 |
| 英文摘要 | DNA damage and consequent mutations initiate the multistep carcinogenic process. Differentiated cells have a reduced capacity to repair DNA lesions, but the biological impact of unrepaired DNA lesions in differentiated lung epithelial cells is unclear. Here, we used a novel organotypic human lung three-dimensional (3D) model to investigate the biological significance of unrepaired DNA lesions in differentiated lung epithelial cells. We showed, consistent with existing notions that the kinetics of loss of simple double-strand breaks (DSBs) were significantly reduced in organotypic 3D culture compared to kinetics of repair in two-dimensional (2D) culture. Strikingly, we found that, unlike simple DSBs, a majority of complex DNA lesions were irreparable in organotypic 3D culture. Levels of expression of multiple DNA damage repair pathway genes were significantly reduced in the organotypic 3D culture compared with those in 2D culture providing molecular evidence for the defective DNA damage repair in organotypic culture. Further, when differentiated cells with unrepaired DNA lesions re-entered the cell cycle, they manifested a spectrum of gross-chromosomal aberrations in mitosis. Our data suggest that downregulation of multiple DNA repair pathway genes in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis. |
| WOS关键词 | MULTIPLY DAMAGED SITES ; BASE EXCISION-REPAIR ; IONIZING-RADIATION ; MAMMALIAN-CELLS ; DIFFERENTIATED CELLS ; ENERGY DEPOSITION ; HUMAN FIBROBLASTS ; CLUSTERED DAMAGE ; ABASIC SITE ; MODEL |
| 资助项目 | National Aeronautics and Space Administration[NNZ07AU42G] ; National Aeronautics and Space Administration Specialized Center of Research[NNX11AC54G] ; National Institutes of Health[CA134991] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000293020000020 |
| 出版者 | OXFORD UNIV PRESS |
| 资助机构 | National Aeronautics and Space Administration ; National Aeronautics and Space Administration Specialized Center of Research ; National Institutes of Health |
| 源URL | [http://119.78.100.186/handle/113462/33930]  |
| 专题 | 近代物理研究所_空间辐射生物研究室 |
| 通讯作者 | Asaithamby, Aroumougame |
| 作者单位 | 1.Chinese Acad Sci, Inst Modern Phys, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China 2.Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Div Mol Radiat Biol, Dallas, TX 75390 USA 3.Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol, Dept Internal Med & Pharmacol, Dallas, TX 75390 USA 4.Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA |
| 推荐引用方式 GB/T 7714 | Ding, Liang-Hao,Story, Michael D.,Minna, John D.,et al. Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture[J]. NUCLEIC ACIDS RESEARCH,2011,39:5474-5488. |
| APA | Ding, Liang-Hao.,Story, Michael D..,Minna, John D..,Shay, Jerry W..,Chen, David J..,...&Delgado, Oliver.(2011).Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture.NUCLEIC ACIDS RESEARCH,39,5474-5488. |
| MLA | Ding, Liang-Hao,et al."Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture".NUCLEIC ACIDS RESEARCH 39(2011):5474-5488. |
入库方式： OAI收割
来源：近代物理研究所
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