Mechanisms of chromosome movement during cell division

细胞分裂过程中染色体运动的机制

• 批准号: RGPIN-2014-04342
• 负责人: Forer, Arthur
• 金额: $ 3.42万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=566457
• 关键词: Mechanisms; chromosome; movement; during; cell

I study the basic mechanisms that control chromosome movements during cell division. Prior to cell division, each chromosome is duplicated; I study how each of the two daughter cells receives one copy of each chromosome. This is important because chromosomes carry genetic information and errors in the distribution of genetic material can cause cell death, birth defects and cancers. Some of our work deals with the forces that move the chromosomes to the two new cells. In cells with pairs of duplicated chromosomes, proper chromosome distribution arises because partner chromosomes line up in the middle of the cell and spindle fibres connect partners to opposite poles. The partners separate simultaneously and move to opposite poles; each spindle fibre shortens as its chromosome moves. This is analogous to pairs of differently coloured boats lined up in the middle of a lake. The 2 boats of each colour are connected by cables to docks on opposite sides of the lake so each dock gets one boat of each colour. Most cell biologists think that boats (chromosomes) are reeled to their docks (poles) by the action of winches at the dock, or winches at the boat, or both. My experiments dispute this idea: we severed the cable (the spindle fibre) with laser or ultraviolet light microbeam irradiations and the boats still moved to their dock. We suggest that the force for movement arises from water currents (from a spindle matrix) and that the cable does not pull the boat but rather guides the boat to the dock. Because the cables (spindle microtubules) resist bending, they resist the movements of the boats, so the speed that a boat moves to its dock is governed by the speed of reeling in the cable. Our proposed experiments study how the spindle matrix produces the force, and how other proteins might be involved. For example, we will stabilise the cables so the winches don’t work (using a drug called paclitaxel) and then sever a cable. If the current produces the force to move the boats, as we believe, the boat should move toward the dock when the cable impediment is removed. Our proposed experiments aim to understand the basic mechanisms that move chromosomes. We also study a less-well understood issue, communication between the boats. Each boat moves to its dock after a starter’s whistle is sounded (a global start signal), and it often is assumed that that is all that is needed. But we have identified various local signals between boats that can alter their motion to their dock. For example, after weaker microbeam irradiation damages the cable between a green boat and its dock, both that boat and its partner green boat (going to the other dock) stop moving: partner boats communicate. In this particular example we have some idea of the mechanism. Boats of the same colour when moving to opposite poles are connected by bungee cords (in cells they are called ‘tethers’), identified by cutting the trailing part of the boat (a trailing arm of the chromosome). The boats keep moving as the severed part of the boat is pulled to the partner boat by the contracting bungee cord. We propose to cut a bungee cord of a boat (with a laser) and then damage the associated cable: if the partners communicate via the bungee cord, communication should stop when we cut a bungee cord so the boat with damaged cable will stop moving but its partner will not. In the other examples of ‘communication’ we do not understand how the coordinated movements arise. Our experiments aim to better understand these communication systems. By understanding them we can better understand how errors arise and how one might ameliorate them.

我研究在细胞分裂过程中控制染色体运动的基本机制。在细胞分裂之前，每条染色体都被复制；我研究了两个子细胞中的每一个是如何接收每个染色体的一个副本的。这一点很重要，因为染色体携带遗传信息，遗传物质分布中的错误可能导致细胞死亡、出生缺陷和癌症。我们的一些工作涉及将染色体移动到两个新细胞的作用力。在具有重复染色体对的细胞中，由于配对染色体在细胞中央排列，纺锤体纤维将配对染色体连接到相反的两极，因此出现了适当的染色体分布。配对细胞同时分离并移动到相反的两极；每个纺锤体纤维随着其染色体的移动而缩短。这类似于在湖中央排成两对不同颜色的船。每种颜色的两艘船通过电缆连接到湖的对岸，因此每个码头都有一艘每种颜色的船。大多数细胞生物学家认为，船只(染色体)是通过码头上的绞车或船上的绞车，或两者兼而有之的作用而卷到码头(杆子)的。我的实验驳斥了这种想法：我们用激光或紫外光微束照射切断了电缆(纺锤形光纤)，但船只仍在向码头移动。我们认为，移动的力来自水流(来自主轴矩阵)，缆索不是拉动船体，而是引导船体到达码头。因为电缆(纺锤形微管)抵抗弯曲，所以它们抵抗船只的移动，所以船只移动到码头的速度取决于电缆的缠绕速度。我们建议的实验研究纺锤体基质如何产生力，以及其他蛋白质可能如何参与其中。例如，我们将稳定电缆，使绞车无法工作(使用一种名为紫杉醇的药物)，然后切断一根电缆。如果如我们所相信的那样，水流产生了移动船只的力量，那么当缆绳障碍物被移除时，船只应该会向码头移动。我们提出的实验旨在了解移动染色体的基本机制。我们还研究了一个不太为人所知的问题，即船与船之间的通信。每艘船在发令员的哨声响起后(全球开始信号)就会移动到自己的码头，人们通常认为这就是所需要的一切。但我们已经确定了船只之间的各种本地信号，这些信号可以改变它们到码头的运动。例如，在较弱的微束辐射损坏了一艘绿船和它的码头之间的电缆后，这艘船和它的伙伴绿船(前往另一个码头)都停止了移动：伙伴船进行通信。在这个特殊的例子中，我们对这种机制有了一些了解。当同一种颜色的船移动到相反的两极时，通过蹦极绳(在细胞中它们被称为‘系绳’)连接，通过切断船的尾部部分(染色体的尾臂)来识别。当船的切断部分被收缩的蹦极绳索拉到伙伴船上时，船继续移动。我们建议(用激光)切断一条船的蹦极绳索，然后损坏相关的电缆：如果合作伙伴通过蹦极绳索进行通信，那么当我们切断蹦极绳索时，通信应该停止，这样电缆损坏的船只将停止移动，但其伙伴不会。在“交流”的其他例子中，我们不理解协调运动是如何产生的。我们的实验旨在更好地理解这些通信系统。通过理解它们，我们可以更好地理解错误是如何产生的，以及如何改进它们。