Three-dimensional Structure, Function and Composition of the Kinetochore

;​R o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o oc。C 4 5 6 7 8 9:；= F Microsoft Word 6.0 Document MSWordDoc6;​本研究的长期目标是阐明有丝分裂过程中染色体运动的分子机制。当高等动物和植物的细胞准备分裂时，它们的DNA从分散状态浓缩成独特的结构，称为染色体。染色体的数量和形状是物种的特征。在有丝分裂开始时，染色体由两个染色体组成，每个染色体都包含一个相同的遗传信息拷贝。在形成后，染色体与纤维双极纺锤体结合，这也在有丝分裂开始时形成，因此，特定染色体的染色体与来自相反纺锤体极点的纤维结合。一旦结合，染色体就会移动到纺锤体的中心。当所有的染色体都在赤道上排成一行时，就会发出一个信号，让染色单体分裂并向相反的纺锤极移动。然后细胞分裂成两个子细胞，每个子细胞接受完整的DNA补充。因此，有丝分裂是使遗传信息的完整拷贝准确地分布到多细胞生物的不同细胞中，并使遗传信息在世代之间传递的过程。因此，它是高等生物至关重要的生命过程之一，否则细胞将受到损害。现代研究表明，染色体运动的大部分动力来自着丝点。后者是在每个染色单体上发现的一种特殊结构，它负责与纺锤体纤维的附着。本提案将使用三维电子显微镜，计算机图形学，改进的标本制备方法，以及视频增强光学显微镜来了解更多关于着丝点如何工作的信息。这个项目将试图确定着丝点是如何构建的，在染色体运动的不同方向上，它是如何与纺锤体纤维相互作用的，以及某些分子成分的精确位置。后者包括已知的或被认为能够沿纺锤体纤维产生运动的分子。这一信息对于评估目前关于染色体运动如何实现的许多假设至关重要。*** ;Oh +' 0 $ H l D H R:\WWUSER\TEMPLATE\NORMAL。[DOT 9420772]雪莉·S·m·S·m·S·m·S·m·S·m·S·m·S·m·S·m·················雪莉·帕克@ 'q:c @ c @ ？~ c @ Microsoft Word 6.0 2；e 3 e j j j j j @ 1 " q T 7 @ j @ j j本研究的长期目标是阐明有丝分裂过程中染色体运动的分子机制。当高等动物和植物的细胞准备分裂时，它们的DNA从分散状态浓缩成独特的结构，称为染色体。染色体的数量和形状是物种的特征。在有丝分裂开始时，染色体由两个染色体组成，每个染色体都包含一个相同的遗传信息拷贝。形成后，染色体结合

; R o o t E n t r y F _ c C o m p O b j b W o r d D o c u m e n t O b j e c t P o o l . c . c 4 5 6 7 8 9 : ; = F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; 9420772 McEwen The long-term objective of the research in this proposal is to elucidate the molecular mechanisms responsible for chromosome movement during mitosis. When cell of higher animals and plants get ready to divide their DNA condenses from its diffuse state into distinct structures called chromosomes. The number and shape of the chromosomes is characteristic of the species. At the onset of mitosis the chromosomes are composed of two chromatics, each of which contains an identical copy of the genetic information. After their formation chromosomes bind to a fibrous bipolar spindle, which also forms at onset of mitosis, such that the chromatics of a given chromosome kind bind to fibers from opposite spindle poles. Once bound the chromosomes move to the center of the spindle. When all of the chromosomes are lined up at the equator, a signal is sent for the chromatids to split apart and move towards opposite spindle poles. The cell then divides in two with each daughter cell receiving a complete complement of DNA. Thus mitosis is the process that enables a complete copy of the genetic i nformation to be accurately distributed to different cells of a multicellular organism, and for genetic information to be transmitted between generations. For this reason it is one of the critically important vital processes of high organisms otherwise the cell would be damaged. Modern research has demonstrated that most of the force for chromosome motions is generated from the kinetochore. The latter is a specialized structure found on each chromatid that is responsible for its attachment to the spindle fibers. This proposal will use three-dimensional electron microscopy, computer graphics, improved methods of specimen preparation, and video enhanced light microscopy to learn more about how the kinetochore work. %%% This project will seek to determine how the kinetochore is constructed, how it interacts with the spindle fibers during chromosome motion in different directions, and precisely where certain molecular components are located. The latter include molecules known or thought to be capable of generating motion along the spindle fibers. This information is critical for evaluating many of the current hypotheses about how chromosome motion is achieved. *** ; Oh +' 0 $ H l D h R:\WWUSER\TEMPLATE\NORMAL.DOT 9420772 Shirley S u m m a r y I n f o r m a t i o n ( 3 Parker Shirley Parker @ 'q:c @ c @ ?~ c @ Microsoft Word 6.0 2 ; e 3 e j j j j j j j @ 1 " q T 7 @ j @ j j j j ~ j j j j : 9420772 McEwen The long-term objective of the research in this proposal is to elucidate the molecular mechanisms responsible for chromosome movement during mitosis. When cell of higher animals and plants get ready to divide their DNA condenses from its diffuse state into distinct structures called chromosomes. The number and shape of the chromosomes is characteristic of the species. At the onset of mitosis the chromosomes are composed of two chromatics, each of which contains an identical copy of the genetic information. After their formation chromosomes bind to