DIPLOCHROMOSOMES: ORIGINS AND SEGREGATION BEHAVIOR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 倍性维持不当(染色体数目)是许多癌细胞类型的标志，并被认为是导致癌细胞种群恶性的原因之一。在许多肿瘤中，四倍体(恰好是正常染色体数量的两倍)先于更严重的退化状态，在这种状态下，单个染色体随机丢失或获得。通过这个项目，我们开始研究在一些四倍体细胞中形成的一种特殊的染色体排列，称为二倍体染色体。 双染色体最常见于肿瘤细胞、用某些毒物处理过的细胞以及姐妹染色单体凝聚力缺陷个体的细胞中。导致二倍体染色体形成的条件还不清楚。细胞分裂时二倍体染色体的分离还没有详细的研究，但在一些生物体中的研究表明，它非常容易出错。因此，二倍体染色体可能有助于CIN表型的发展，并解释了四倍体与恶性肿瘤之间的联系。 二倍体染色体存在的意义以及形成它们的因素还没有被研究过。这个项目包括一些实验，使我们能够开始解决这两个问题。我们还将确定细胞分裂时二倍体染色体的分离行为。通过这些实验，我们将加深对某些人类发育障碍的病因学的理解，在这些疾病中，姐妹染色单体凝聚力降低会导致含有双染色体的细胞的形成和癌症发病率的增加。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Improper maintenance of ploidy (chromosome number) is a hallmark of many cancer cell types, and is thought to contribute to the malignancy of cancer cell populations. In a number of tumors tetraploidy (exactly twice the normal chromosome number) precedes a more degenerate state, in which individual chromosomes are lost or gained at random. With this project we begin an investigation of a particular chromosomal arrangement that forms in some tetraploid cells, called a diplochromosome. Diplochromosomes are most commonly seen in tumor cells, in cells that have been treated with certain kinds of poisons, and in cells from individuals with defects in sister chromatid cohesion. The conditions that lead to diplochromosome formation are not understood. The segregation of diplochromosomes when cells divide has not been investigated in detail, but studies in some organisms suggest that it is highly error-prone. Thus diplochromosomes might contribute to development of the CIN phenotype, and explain the connection between tetraploidy and malignancy. The significance of the presence of diplochromosomes, and the factors that contribute to their formation, have not been investigated. This project includes experiments that will allow us to begin to address both issues. We will also determine the segregation behavior of diplochromosomes at cell division. With these experiments we will increase our understanding of the etiology of certain human developmental disorders, in which decreased sister chromatid cohesion leads both to formation of diplochromosome-containing cells and increased incidence of cancer.