Extrachromosomal circular DNA of tandemly repeated genomic sequences in Drosophila

Extrachromosomal circular DNA of tandemly repeated genomic sequences in Drosophila
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DOI:
10.1101/gr.907603
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发表时间:
2003-06-01
期刊:
影响因子:
7
通讯作者:
Segal, D
Segal, D
中科院分区:
生物学1区
文献类型:
--
作者:
Cohen, S;Yacobi, K;Segal, D

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基因组可塑性的特征之一是染色体外环状 DNA (eccDNA) 的存在。这种 DNA 存在于从酵母到人类的各种真核生物中,其水平会因接触致癌物而升高。 eccDNA 大小不同且由染色体序列组成。在本研究中,我们使用二维凝胶电泳来检测和表征果蝇中的 eccDNA。我们在苍蝇的整个生命周期中发现了 eccDNA。这些分子占总重复 DNA 含量的 10%,其大小范围为 20 kb。 eccDNA 群体包含串联重复基因的环状多聚体,例如组蛋白、rDNA、星状蛋白和星状蛋白抑制子。着丝粒异染色质序列的多聚体也包含在 eccDNA 中。我们的研究结果与以下假设一致:直接串联重复之间的分子内同源重组是 eccDNA 形成的最喜欢的机制。 MMS 处理野生型幼虫后 eccDNA 水平增加,与培养的哺乳动物细胞中观察到的现象一致。这首次表明在整个生物体中诱变剂诱导的 eccDNA 形成。 okra、mus309 和 mei41 基因的突变在正常条件下或诱变剂处理后不会影响 eccDNA,这意味着 eccDNA 的形成与已知的 DNA 修复途径不同。
One characteristic of genomic plasticity is the presence of extrachromosomal circular DNA (eccDNA). This DNA is found in various eukaryotes from yeast to humans, and its levels are elevated by exposure to carcinogens. eccDNA is heterogeneous in size and composed of chromosomal sequences. In this Study we used two-dimensional gel electrophoresis to detect and characterize eccDNA in Drosophila. We found eccDNA throughout the fly's life cycle. These molecules comprise Lip to 10% of tile total repetitive DNA content, and their size ranges from 20 kb. The eccDNA Population contains circular multimers of tandemly repeated genes such as histones, rDNA, Stellate, and the Suppressor of Stellate. Multimers of centromeric heterochromatin sequences are included in eccDNA as Well. Our findings are consistent with the hypothesis that intramolecular homologous recombination between direct tandem repeats is a favorite mechanism for eccDNA formation. The level of eccDNA increased following MMS treatment of wild-type larvae, consistent with phenomena observed in Cultured mammalian cells. This shows mutagen-induced eccDNA formation in the context of the whole organism for the first time. Mutations in the genes okra, mus309, and mei41 did not affect eccDNA under normal conditions or following mutagen treatment, implying that eccDNA formation is different from known pathways of DNA repair.