Molecular genetics - MaRX: An approach to genetics in mammalian cells

Molecular genetics - MaRX: An approach to genetics in mammalian cells
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DOI:
10.1126/science.283.5405.1129
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发表时间:
1999-02-19
期刊:
影响因子:
56.9
通讯作者:
Beach, D
Beach, D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hannon, GJ;Sun, PQ;Beach, D

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遗传学方法是阐明人们知之甚少的生物过程的最直接的方法。最早的此类努力之一--Beadle和Tatum(1)关于代谢途径遗传学的里程碑式研究--建立了有影响力的“一个基因,一种酶”假说。在随后的几十年里,酿酒酵母和S。pombe成为了首要的遗传模型。然而,经常吹捧的“酵母遗传学的力量”并没有完全实现,直到经典技术与用重组DNA方法操纵生物体的能力相结合(2-4)。因此,今天使酵母成为最具特征的真核生物的工具被设想出来。然而,这些工具有其局限性:积累人类序列数据揭示了许多在酵母中不存在的基因。从酵母到人类的飞跃是如何实现的?为了解决这个问题,我们试图将遗传方法应用于哺乳动物或其可操纵的替代品,培养的哺乳动物细胞。我们没有创造一种在技术上反映酵母方法的遗传方法,而是开发了一种与哺乳动物生物学类似的遗传方法-马克思系统。
A genetic approach is the most direct way to elucidate biological processes that are poorly understood. One of the first such efforts—the landmark study of Beadle and Tatum (1) on the genetics of metabolic pathways—established the influential “one gene, one enzyme” hypothesis. In subsequent decades, the yeasts Saccharomyces cerevisiae and S. pombe became the premier genetic models. The oft-touted “power of yeast genetics” was not fully realized, however, until classical techniques were combined with an ability to manipulate the organisms with recombinant DNA methods (2–4). Thus were conceived the tools that today make yeasts the best-characterized eukaryotes. These tools, however, have limitations: accumulating human sequence data reveals many genes that are not represented in yeast. How can the leap be made from yeast to human?To solve this problem, we sought to apply genetic methods to mammals or their manipulable surrogates, cultured mammalian cells. Rather than creating a genetic methodology that technically mirrors the approach in yeast, we developed one with comparable genetic access to mammalian biology—the MaRX system.