The nonhomologous DNA end joining pathway is important for chromosome stability in primary fibroblasts
The nonhomologous DNA end joining pathway is important for chromosome stability in primary fibroblasts
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DOI：
10.1016/s0960-9822(00)80123-2
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发表时间：
1999-12-16
期刊：
影响因子：
9.2
通讯作者：
Lieber, MR
中科院分区：
文献类型：
--
作者：
Karanjawala, ZE;Grawunder, U;Lieber, MR
有两种类型的染色体不稳定，结构不稳定性和数量不稳定性，这在癌症中很重要。许多结构异常可能涉及双链DNA(DsDNA)断裂。非同源DNA末端连接(NHEJ)和同源重组是修复dsDNA断裂的主要途径。在细胞周期的G0、G1和S早期，NHU是修复双链DNA断裂的主要途径[1]，KU86和DNA连接酶IV是NHU途径中的两个主要蛋白质。我们检测了来自小鼠的原代真皮成纤维细胞(野生型，Ku86(+/-)，Ku86(-/-)和DNA连接酶IV+/-)的染色体断裂。与野生型小鼠相比，来自Ku86(+/-)或DNA连接酶IV+/-小鼠的成纤维细胞的染色体断裂频率更高。来自Ku86(-/-)小鼠的成纤维细胞有更高水平的染色体断裂。来自相同动物的原代Pre-B细胞没有显示出明显的染色体断裂积累。相反，前B细胞表现出更多的细胞死亡。这些研究表明，染色体断裂频繁发生，而NHU需要修复这种持续的自发损伤。(C)1999爱思唯尔科学有限公司。保留所有权利。
There are two types of chromosome instability, structural and numerical, and these are important in cancer. Many structural abnormalities are likely to involve double-strand DNA (dsDNA) breaks. Nonhomologous DNA end joining (NHEJ) and homologous recombination are the major pathways for repairing dsDNA breaks. NHU is the primary pathway for repairing dsDNA breaks throughout the G0, G1 and early S phases of the cell cycle [1], Ku86 and DNA ligase IV are two major proteins in the NHU pathway. We examined primary dermal fibroblasts from mice (wild type, Ku86(+/-), Ku86(-/-), and DNA ligase IV+/-) for chromosome breaks. Fibroblasts from Ku86(+/-) or DNA ligase IV+/- mice have elevated frequencies of chromosome breaks compared with those from wild-type mice. Fibroblasts from Ku86(-/-) mice have even higher levels of chromosome breaks. Primary pre-B cells from the same animals did not show significant accumulation of chromosome breaks. Rather the pre-B cells showed increased cell death. These studies demonstrate that chromosome breaks arise frequently and that NHU is required to repair this constant spontaneous damage. (C) 1999 Elsevier Science Ltd. All rights reserved.