Mai Sabine, Garini Yuval
Manitoba Institute of Cell Biology, University of Manitoba, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
Cell Cycle. 2005 Oct;4(10):1327-31. doi: 10.4161/cc.4.10.2082. Epub 2005 Oct 5.
The three-dimensional (3D) organization of the normal interphase nucleus permits the regulated completion of transcription and replication and assures proper chromosome organization. Aberrations from the normal 3D structural order of the nucleus are found in tumor cells. When examining the 3D organization of telomeres in nuclei of normal and tumor cells, we found that telomeres of normal nuclei do not overlap, while telomeres of tumor cells form aggregates of various numbers and sizes. To understand how such changes occur and what their implications are we have recently examined the role of the oncoprotein c-Myc in inducing changes in the 3D nuclear organization of telomeres. We found that c-Myc remodels the organization of telomeres and chromosomes in the interphase nucleus. It induces the formation of telomeric aggregates and fusions that are followed by breakage-bridge fusion cycles, and lead to the onset of chromosomal rearrangements that are typical of tumor cells.
正常间期细胞核的三维（3D）结构有助于转录和复制的有序完成，并确保染色体的正确组织。肿瘤细胞中存在与细胞核正常3D结构顺序的偏差。在检查正常细胞和肿瘤细胞核中端粒的3D组织时，我们发现正常细胞核的端粒不重叠，而肿瘤细胞的端粒形成了各种数量和大小的聚集体。为了了解这些变化是如何发生的以及它们的意义是什么，我们最近研究了癌蛋白c-Myc在诱导端粒3D核组织变化中的作用。我们发现c-Myc重塑了间期细胞核中端粒和染色体的组织。它诱导端粒聚集体和融合的形成，随后是断裂-桥接-融合循环，并导致肿瘤细胞典型的染色体重排的发生。
