Abstract:
Collaborative studies open doors to breakthroughs otherwise unattainable by any one laboratory alone. Here we describe the initial collaboration between the Griffith and de Lange laboratories that led to thinking about the telomere as a DNA template for homologous recombination, the proposal of telomere looping, and the first electron micrographs of t-loops. This was followed by collaborations that revealed t-loops across eukaryotic phyla. The Griffith and Tomáška/Nosek collaboration revealed circular telomeric DNA (t-circles) derived from the linear mitochondrial chromosomes of nonconventional yeast, which spurred discovery of t-circles in ALT-positive human cells. Collaborative work between the Griffith and McEachern labs demonstrated t-loops and t-circles in a series of yeast species. The de Lange and Zhuang laboratories then applied super-resolution light microscopy to demonstrate a genetic role for TRF2 in loop formation. Recent work from the Griffith laboratory linked telomere transcription with t-loop formation, providing a new model of the t-loop junction. A recent collaboration between the Cesare and Gaus laboratories utilized super-resolution light microscopy to provide details about t-loops as protective elements, followed by the Boulton and Cesare laboratories showing how cell cycle regulation of TRF2 and RTEL enables t-loop opening and reformation to promote telomere replication. Twenty years after the discovery of t-loops, we reflect on the collective history of their research as a case study in collaborative molecular biology.
摘要:
合作研究为任何一个实验室都无法实现的突破打开了大门。在这里,我们描述了Griffith和deLange实验室之间的最初合作,这些合作导致了将端粒作为同源重组的DNA模板的思考,端粒循环的提议,和t环的第一张电子显微照片。随后是合作,揭示了整个真核细胞门的t环。Griffith和Tomáška/Nosek的合作揭示了源自非常规酵母线性线粒体染色体的环状端粒DNA(t环),这刺激了ALT阳性人类细胞中t-圈的发现。Griffith和McEachern实验室之间的合作工作证明了一系列酵母物种中的t环和t环。然后,deLange和Zhuang实验室应用超分辨率光学显微镜来证明TRF2在环路形成中的遗传作用。格里菲斯实验室最近的工作将端粒转录与t环形成联系起来,提供了一种新的t环连接模型。Cesare和Gaus实验室之间最近的合作利用超分辨率光学显微镜来提供有关t环作为保护元素的详细信息。其次是Boulton和Cesare实验室,展示了TRF2和RTEL的细胞周期调节如何使t环开放和重整促进端粒复制。在发现t环20年后,作为合作分子生物学的案例研究,我们反思了他们研究的集体历史。