CHROMOSOME MOVEMENT IN PROMETAPHASE

在染色体错位的情况下，正常的体细胞 在中国被捕 M期。这个监视系统或细胞周期检查点 防止出现 染色体过多或过少的子代细胞的产生。 这个 这项工作的长期目标是在这里提出申请 划定 调控有丝分裂细胞的信号通路的所有步骤 循环 检查站。工作假说是，阻止信号 起病 后期发源于“放松的”动素，那些缺乏的 稳定 微管附着物。机械张力的传授 依附 有丝分裂纺锤体微管的改变导致构象变化 在……里面 动核组件并关闭检查点信号。这个 着丝粒上的检查点信号涉及蛋白质 磷酸化 被3F3/2单抗识别。的具体目标 这 建议是：剖析3F3/2的分子性质 磷酸表位及其如何参与检查点的确定 调控，识别产生3F3/2的激酶 磷表位 并确定它在细胞周期中是如何调节的，以及 最后， 确定张力是如何调节激酶活性的。M相 检查站在确保平等隔离方面发挥着至关重要的作用 有丝分裂和减数分裂中的染色体。在癌症中，细胞周期 检查点 经常是有缺陷的。在某些情况下，这实际上可能会增强 这个 通过肿瘤治疗诱导细胞凋亡。然而，染色体 失衡也会导致癌症的进展。 肿瘤。 在生殖细胞成熟过程中，染色体不平衡在 减数分裂 是导致出生缺陷的重要原因。了解M如何 相位 检查站是受监管的承诺，新的理解方式和 小说 干预人类癌症和出生缺陷的途径。

In the presence of misaligned chromosomes, normal somatic cells arrest in M phase. This surveillance system or cell cycle checkpoint prevents the generation of progeny cells with too many or too few chromosomes. The long-term objective of this work proposed here application is delineating all steps of the signaling pathways that regulate mitotic cell cycle checkpoints. The working hypothesis is that signals blocking the onset of anaphase emanate from "relaxed" kinetochores, those lacking stable microtubule attachments. Mechanical tension imparted by the attachment of mitotic spindle microtubules leads to conformational changes of in kinetochore components and turns off the checkpoint signal. The checkpoint signal at the kinetochore involves protein phosphorylation recognized by the 3F3/2 monoclonal antibody. The specific aims of this proposal are: dissecting the molecular nature of the 3F3/2 phosphoepitope, and determining how it participates in checkpoint regulation, identifying the kinase that creates the 3F3/2 phosphoepitope and determining how it is regulated during the cell cycle, and lastly determining how kinase activity is regulated by tension. M phase checkpoints play an essential role in assuring equal segregation of chromosomes in mitosis and meiosis. In cancer, cell cycle checkpoints are often faulty. In some instances this may, in fact, potentiate the induction of apoptosis by tumor therapies. However, chromosome imbalances also contribute to the progression of malignancy in tumors. In germ cell maturation, chromosomal imbalances induced during meiosis are a significant cause of birth defects. Understanding how the M phase checkpoints are regulated promises new ways of understanding and novel avenues for intervention in human cancer and birth defects.