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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=610974
• 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，每条染色体都进行复制;我研究两个子细胞中的每一个如何接收每条染色体的一个副本。这很重要，因为染色体携带遗传信息，遗传物质分布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力。在具有成对的复制染色体的细胞中，正确的染色体分布出现，因为伴侣染色体在细胞中间排成一行，纺锤体纤维将伴侣连接到相反的两极。配偶体同时分离并移向相反的两极;每个纺锤体纤维随着其染色体的移动而缩短。这类似于成对的不同颜色的船在湖中央排成一行。每种颜色的2艘船通过电缆连接到湖两侧的码头，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（染色体）是通过码头上的绞盘或船上的绞盘或两者的作用被卷到码头（杆子）上的。我的实验反驳了这一观点：我们用激光或紫外线微束照射切断了电缆（纺锤纤维），船仍然可以移动到码头。我们认为，运动的力量来自水流（来自主轴矩阵），缆绳并不拉动船，而是将船引导到码头。因为缆绳（纺锤微管）抵抗弯曲，它们抵抗船的运动，所以船移动到码头的速度由缆绳的卷取速度决定。我们提出的实验研究纺锤体基质如何产生力，以及其他蛋白质如何参与其中。例如，我们将稳定电缆，使绞车不工作（使用一种药物称为紫杉醇），然后切断电缆。如果水流产生的力量使船移动，正如我们所相信的那样，当电缆障碍物被移除时，船应该向码头移动。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了解的问题，船只之间的通信。每艘船在发令员的哨声响起后（全球启动信号）移动到其码头，通常认为这就是所需要的。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，在较弱的微束照射损坏了绿色船和其码头之间的电缆后，该船及其伙伴绿色船（前往另一个码头）都停止移动：伙伴船进行通信。在这个特殊的例子中，我们对这个机制有了一些了解。当同一颜色的船移动到相反的两极时，由蹦极绳连接（在细胞中，它们被称为“系绳”），通过切割船的尾部（染色体的拖曳臂）来识别。当船的切断部分被收缩的蹦极绳索拉到伙伴船时，船继续移动。我们建议用激光切断船的蹦极绳，然后损坏相关的电缆：如果合作伙伴通过蹦极绳进行通信，当我们切断蹦极绳时，通信应该停止，因此电缆损坏的船将停止移动，但其合作伙伴不会。在其他“沟通”的例子中，我们不明白协调的运动是如何产生的。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，以及如何改善它们。