DIPLOCHROMOSOMES: ORIGINS AND SEGREGATION BEHAVIOR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 倍性（染色体数目）的不适当维持是许多癌细胞类型的标志，并且被认为有助于癌细胞群体的恶性。 在许多肿瘤中，四倍体（正好是正常染色体数目的两倍）出现在更退化的状态之前，在这种状态下，单个染色体随机丢失或获得。 在这个项目中，我们开始研究在某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。 二倍体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缺陷的个体细胞。 导致二倍体染色体形成的条件尚不清楚。 细胞分裂时二倍体染色体的分离还没有被详细研究，但在一些生物中的研究表明，它是非常容易出错的。因此，二倍体染色体可能有助于CIN表型的发展，并解释四倍体和恶性肿瘤之间的联系。 二倍体染色体存在的意义，以及促成其形成的因素尚未研究。 这个项目包括实验，将使我们能够开始解决这两个问题。 我们还将确定二倍体染色体在细胞分裂时的分离行为。 通过这些实验，我们将增加我们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导致含二倍体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.