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-2019-06299
• 负责人: Forer, Arthur
• 金额: $ 3.06万
• 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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=715991
• 关键词: Mechanisms; chromosome; movement; during; cell

I study the basic mechanisms that control chromosome movements during cell division. Chromosomes are duplicated in the nucleus; then one copy of each is distributed to each daughter cell during cell division. Errors can cause cell death, birth defects and cancers. Chromosomes are distributed to daughter cells by the mitotic spindle, a temporary structure used solely to move chromosomes. First the duplicated chromosomes line up in the middle of the spindle. Spindle fibres connect them to opposite spindle poles, analogous to pairs of differently coloured boats lined up in the middle of a lake with the two boats (chromosomes) of each colour connected by a cable (spindle fibre) to a dock (spindle pole) on opposite sides of the lake. Each of the two docks gets one boat of each colour. We study the forces that move chromosomes (boats) to their poles (docks). Most cell biologists think that boats are reeled in to their docks by winches at the dock, or winches at the boat, or both. Our experiments dispute this idea. We sever the cables (spindle fibres) with a laser microbeam and the boats still move to their dock. We suggest that the force for movement arises from water currents (from a spindle matrix). We reached the same conclusion from experiments in which the cables were dissolved (with a drug) and the boats then rapidly moved to one dock. Having boats move without cables allows us to identify and study the water (spindle matrix) components that may produce the force. We also study communication between the chromosomes (boats). Each boat moves to its dock after a starter's whistle sounds (a global start signal). It often is assumed that this is all that is needed, but we have identified signals between boats that alters their motions to their docks. For example, boats of the same colour moving to opposite docks coordinate their speeds: when we weakly damage (but do not sever) the cable between a boat and its dock, both that boat and its partner boat (going to the other dock) stop moving. In this example the communication agents are “tethers”, universal spindle components that we recently uncovered, analogous to bungee cords that connect boats of the same colour. When we cut a bungee cord (tether) with a laser, and then weakly damage the cable, communication between partner boats stops: the boats move independently. In other examples of communication there are no physical connections between the chromosomes. The overall goal of our research program is to understand the force production and inter-chromosome communication systems. Our short-term goal is to identify the non-cable (non-spindle fibre) force elements and to characterise the tethers and other elements of inter-chromosome coordination. Importance: By knowing how chromosome movements occur and are controlled we can better understand the causes of errors in chromosome distributions that cause birth defects and cancers; such understanding can lead to preventions.

我研究在细胞分裂过程中控制染色体运动的基本机制。染色体在细胞核中复制，然后在细胞分裂期间，每个染色体的一个副本被分配给每个子细胞。错误会导致细胞死亡、出生缺陷和癌症。 染色体通过有丝分裂纺锤体分配给子细胞，有丝分裂纺锤体是一种仅用于移动染色体的临时结构。首先，复制的染色体在纺锤体的中间排成一排。纺锤纤维将它们连接到相对的纺锤杆上，类似于在湖中央排成对的不同颜色的小船，每种颜色的两条船(染色体)通过电缆(纺锤纤维)连接到湖两侧的码头(纺锤杆)。两个码头各有一艘船，每种颜色各一艘。 我们研究将染色体(船)移动到它们的极点(码头)的力。大多数细胞生物学家认为，船只是通过码头上的绞车或船上的绞车，或者两者兼而有之才被卷到码头的。我们的实验对这一观点提出了异议。我们用激光微束切断了电缆(纺锤形光纤)，但船只仍在向码头移动。我们认为，运动的力来自水流(来自纺锤母体)。我们从实验中得出了同样的结论，在实验中，电缆被(用药物)溶解，然后船只迅速移动到一个码头。让船在没有缆绳的情况下移动，使我们能够识别和研究可能产生力的水(主轴矩阵)组件。 我们还研究染色体之间的通讯(BOTS)。在发令员的哨声响起(全球开始信号)后，每艘船都会移动到自己的码头。人们通常认为这就是所需要的一切，但我们已经识别出船只之间的信号会改变它们到码头的运动。例如，相同颜色的船只移动到对面码头时，它们的速度是协调的：当我们微弱地损坏(但不切断)一艘船和它的码头之间的电缆时，这艘船和它的伙伴船(去往另一个码头)都会停止移动。在这个例子中，通信代理是“系绳”，即我们最近发现的通用主轴部件，类似于连接相同颜色船只的蹦极绳索。当我们用激光切断一根蹦极绳索(系绳)，然后微弱地损坏电缆时，伙伴船之间的通信就会停止：船独立移动。在其他交流的例子中，染色体之间没有物理联系。我们研究计划的总体目标是了解力量的产生和染色体间的通讯系统。我们的短期目标是确定非缆索(非纺锤形纤维)的作用力元素，并描述系绳和其他染色体间协调元素的特征。 重要：通过了解染色体运动是如何发生和控制的，我们可以更好地了解导致出生缺陷和癌症的染色体分布错误的原因；这种理解可以导致预防。