Abstract
Telomeres, the terminal chromosomal structure crucial for maintaining genomic integrity, shorten with deoxyribonucleic acid replications in most human somatic cells. Chromosomes carrying critically short telomeres tend to form end-to-end fusions, which are subject to breakage during cell division. However, it remains obscure how such telomere-mediated fusions are resolved during the process of immortalization, which is an early and indispensable step toward cancer. It has been hypothesized that the breakage could occur at either the microtubule or chromatid, causing numerical or structural chromosome instability, respectively. In this paper, we show that although the distributions of chromosomal segment losses or gains involved in structural aberrations were significantly correlated with the profiles of critically short telomeres in human epithelial cells undergoing immortalization, no such association was detected for whole-chromosome losses or gains in either metaphase or interphase cells. By distinguishing between homologues, we further showed that the specific homologues with critically short telomeres and frequent end-to-end fusions were not preferentially involved in respective whole-chromosome losses or gains. Our data therefore demonstrate that microtubule breakage is not a major mechanism for resolving chromosomal end-to-end fusions in human cells undergoing immortalization. An important implication of this finding is that microtubule–kinetochore attachment is stronger than the chromosome structure.
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Acknowledgments
We thank Drs. P.M. Lansdorp and S.S.S. Poon (BC Cancer Research Center, Canada) for the Q-FISH software (TFL-TELO). This study was supported by grants from the Research Grants Council of Hong Kong Special Administrative Region, China (Project No. HKU 7385/03M and HKU 7556/06M), and a Seed Funding research grant from the University of Hong Kong URC (200411159061) to ALM Cheung, as well as a research grant from the University of Hong Kong CRCG (200507176189) to W Deng and ALM Cheung. We thank Jenny Cheung, Tony Chan, Alla Li, and Liang Hu for technical assistance and Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, for use of SKY facilities.
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Deng, W., Tsao, S.W., Guan, XY. et al. Microtubule breakage is not a major mechanism for resolving end-to-end chromosome fusions generated by telomere dysfunction during the early process of immortalization. Chromosoma 116, 557–568 (2007). https://doi.org/10.1007/s00412-007-0120-x
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DOI: https://doi.org/10.1007/s00412-007-0120-x