Building synthetic chromosomes from natural DNA.

Building synthetic chromosomes from natural DNA.
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DOI:
10.1038/s41467-023-44112-2
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发表时间:
2023-12-20
影响因子:
16.6
通讯作者:
Ehrenreich, Ian M.
Ehrenreich, Ian M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Coradini, Alessandro L. V.;Ville, Christopher Ne;Krieger, Zachary A.;Roemer, Joshua;Hull, Cara;Yang, Shawn;Lusk, Daniel T.;Ehrenreich, Ian M.

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重新合成染色体成本高,耗时长,限制了其在研究和生物技术中的应用。从自然成分构建合成染色体是一种未开发的选择,具有许多潜在的应用。在本文中,我们报道了一种利用酵母的天然成分构建合成染色体的方法——创建(克隆、重编程和组装天然基因组DNA)。创造需要克隆自然染色体的片段,然后以可编程的方式将它们组装成可以取代细胞中天然染色体的合成染色体。我们使用create来合成重组菌株和物种之间的染色体,修改染色体结构,并删除许多连接的,不相邻的区域,总计一条染色体的39%。多重删除实验表明,通过合成染色体与原染色体之间的重组,创造也可以从合成染色体设计中的缺陷中恢复过来。创造促进了染色体合成在各种生物学问题上的应用。从天然成分构建合成染色体是一种尚未开发的替代重新合成染色体,可能有许多潜在的应用。在本文中,作者报告了一种利用酵母的天然成分构建合成染色体的方法。
De novo chromosome synthesis is costly and time-consuming, limiting its use in research and biotechnology. Building synthetic chromosomes from natural components is an unexplored alternative with many potential applications. In this paper, we report CReATiNG (Cloning, Reprogramming, and Assembling Tiled Natural Genomic DNA), a method for constructing synthetic chromosomes from natural components in yeast. CReATiNG entails cloning segments of natural chromosomes and then programmably assembling them into synthetic chromosomes that can replace the native chromosomes in cells. We use CReATiNG to synthetically recombine chromosomes between strains and species, to modify chromosome structure, and to delete many linked, non-adjacent regions totaling 39% of a chromosome. The multiplex deletion experiment reveals that CReATiNG also enables recovery from flaws in synthetic chromosome design via recombination between a synthetic chromosome and its native counterpart. CReATiNG facilitates the application of chromosome synthesis to diverse biological problems. Building synthetic chromosomes from natural components is an unexplored alternative to de novo chromosome synthesis that may have many potential applications. In this paper, the authors report CReATiNG, a method for constructing synthetic chromosomes from natural components in yeast.
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