David H. Dressler 1941-2014.
David H. Dressler 1941-2014.
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大卫·H·德雷斯勒，1941-2014。
DOI：
10.1038/ng.3099
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发表时间：
2014
期刊：
影响因子：
30.8
通讯作者：
Potter,Huntington
中科院分区：
文献类型：
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作者：
Potter,Huntington
2014年是遗传学研究中一个不幸的里程碑：两位科学家共同澄清了我们对基因重组的理解，罗宾·霍利迪和大卫·德雷斯勒分别于今年4月9日和5月27日去世。大卫·德雷斯勒1941年出生于俄亥俄州的辛辛那提，1963年毕业于哥伦比亚大学，随后进入哈佛大学读研究生，加入了由詹姆斯·沃森领导的发展中的分子生物学小组，1969年获得博士学位。大卫的论文实验表明，Φ DNA复制中间体并不像当时的教条那样是一个单位基因组长度的双链环，而是包括一个更长的线性正链，它是从一个环状负链模板以连续的方式合成的。这一发现导致了现在建立的DNA复制的“滚环模型”，但并非没有挫折。困难出现了，因为Φ X DNA复制研究的公认领导者罗伯特·辛谢默（Robert Sinsheimer）推广了标准模型。大卫的正式导师接受了这一权威，不相信大卫的结果，并终止了他的奖学金。然后，沃尔特吉尔伯特给了大卫空间和资源，让他继续进行实验，这些实验证明了滚环模型，也是不对称生长点的第一个证明，其中一个子链连续延伸，第二个子链不连续延伸。今天，我们认为这些结果是不言自明的，但他们在发现的时候是非常有争议的。大卫继续他对DNA的研究，使用分子生物学和电子显微镜来证明滚环模型在非洲爪蟾核糖体DNA扩增中的应用，噬菌体T7 DNA复制过程中的双向和不对称生长点，噬菌体G4中DNA复制起点的结构和腺病毒DNA末端的反向重复序列。1972年我加入大卫的实验室时，表达了对研究重组的兴趣，于是我们选择了一种新发现的具有单一限制位点的土方ichiacoliplasma作为实验系统。我们通过电子显微镜观察到的许多双倍大小的DNA分子开始时具有8字形的构型，并在消化后变为X形（我们称之为“X形”）。事实上，chi形式只存在于RecA阳性细胞中，这使它们成为重组中间体。然后，部分变性表明，两个重组的双螺旋交换并重新连接单链，产生了罗宾·霍利迪在1964年提出的重组模型的一部分，他在真菌遗传研究的基础上开发了重组模型。霍利迪连接的物理演示，从而巩固了霍利迪模型及其后续的修改作为原核生物和真核生物的基础。除了致力于研究之外，大卫还是一位热心的教师。与詹姆斯沃森、圭多·圭多蒂和
The year 2014 represents an unfortunate landmark in the study of genetics: two scientists who together clarified our understanding of genetic recombination, Robin Holliday and David Dressler, passed away this year, on 9 April and 27 May, respectively. David Dressler was born in Cincinnati, Ohio, in 1941, graduated from Columbia University in 1963 and went on to graduate school at Harvard University, joining the developing molecular biology group headed by James Watson and earning his doctorate in 1969. David’s dissertation experiments showed that the ΦΧ DNA replication intermediate was not, as was dogma at the time, a double-stranded circle of unit genome length but included a much longer linear positive strand that was synthesized in a continuous fashion from a circular negativestrand template. This discovery led to the now established ‘rolling circle model’of DNA replication but not without setbacks. Difficulties arose because Robert Sinsheimer, the avowed leader of ΦΧ DNA replication studies, promoted the standard model. Accepting this authority, David’s official mentor disbelieved David’s results and terminated his fellowship. Walter Gilbert then gave David the space and resources to continue the experiments that proved the rolling circle model and were one of the first demonstrations of the asymmetric growing point, in which one daughter strand is elongated continuously and the second daughter strand is elongated discontinuously. Today we view these results as axiomatic, but they were highly controversial at the time of their finding.David continued his research on DNA, using molecular biology and electron microscopy to demonstrate the application of the rolling circle model to ribosomal DNA amplification in Xenopus, the bidirectional and asymmetric growing points during the replication of bacteriophage T7 DNA, the structure of the origin of DNA replication in phage G4 and the inverted repeats on the ends of adenovirus DNA. When I joined David’s laboratory in 1972, I expressed interest in studying recombination, and we chose as the experimental system one of the newly discovered Escherichiacoliplasmids that had a single restriction site. The many double-sized DNA molecules we observed through the electron microscope started out with the configuration of a figure eight and changed upon digestion to an X shape (which we termed a ‘chi form’). The fact that chi forms were only present in RecA-positive cells established them as recombination intermediates. Partial denaturation then showed that the two recombining double helices had exchanged and religated single strands to generate the very structure that Robin Holliday had proposed in 1964 as part of the recombination model that he developed on the basis of genetic studies in fungi. The physical demonstration of the Holliday junction thus solidified the Holliday model and its subsequent modifications as fundamental to both prokaryotes and eukaryotes. In addition to being dedicated to research, David was also a devoted teacher. Together with James Watson, Guido Guidotti and