Mouse major satellite DNA is prone to eccDNA formation via DNA Ligase IV-dependent pathway
Mouse major satellite DNA is prone to eccDNA formation via DNA Ligase IV-dependent pathway
复制标题
DOI：
10.1038/sj.onc.1209485
复制
发表时间：
2006-08-03
期刊：
影响因子：
8
通讯作者：
Lavi, S.
中科院分区：
文献类型：
--
作者：
Cohen, Z.;Bacharach, E.;Lavi, S.
染色体外环状DNA（eccDNA或spcDNA）水平升高与基因组不稳定性和衰老密切相关。尽管进行了广泛的研究，但其在哺乳动物细胞中产生的机制尚不清楚。我们在这里报告，小鼠主要卫星DNA（MSD）是易于eccDNA的形成，所产生的分子是multimeres的基本重复。在B16小鼠黑色素瘤细胞中，染色体外环状主要卫星（ECMS）DNA构成了eccDNA的大部分，并且在其他小鼠细胞中高度丰富。这些分子的产生在增殖细胞中增强，表明与DNA复制相关的过程参与了它们的出现。使用siRNA技术，我们表明DNA连接酶IV参与ECMS合成。基于我们的研究结果，我们提出了一种新的两步模型eccDNA在哺乳动物细胞中的形成。
Elevated levels of extrachromosomal circular DNA (eccDNA or spcDNA) are closely associated with genomic instability and aging. Despite extensive studies, the mechanism of its generation in mammalian cells is unknown. We report here that mouse major satellite DNA (MSD) is prone to eccDNA formation and that the resulting molecules are multimeres of the basic repeat. Extrachromosomal circular major satellite (ECMS) DNA constitutes the majority of eccDNA in B16 mouse melanoma cells and is highly abundant in other mouse cells. Production of these molecules is enhanced in proliferating cells, suggesting that processes associated with DNA replication are involved in their appearance. Using siRNA technique we show that DNA Ligase IV is engaged in ECMS synthesis. Based on our findings we propose a novel two-step model for eccDNA formation in mammalian cells.