caa a22 4500 46320946X CHVBK 20180405153136.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s00412-007-0120-x doi (NATIONALLICENCE)springer-10.1007/s00412-007-0120-x Microtubule breakage is not a major mechanism for resolving end-to-end chromosome fusions generated by telomere dysfunction during the early process of immortalization [Elektronische Daten] [W. Deng, S. Tsao, X.-Y. Guan, A. Cheung] 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. Springer-Verlag, 2007 Deng W. Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China aut Tsao S. Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China aut Guan X.-Y Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China aut Cheung A. Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China aut Chromosoma Springer-Verlag 116/6(2007-12-01), 557-568 0009-5915 116:6<557 2007 116 412 https://doi.org/10.1007/s00412-007-0120-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00412-007-0120-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Deng W. Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China aut NATIONALLICENCE 700 1- Tsao S. Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China aut NATIONALLICENCE 700 1- Guan X.-Y Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China aut NATIONALLICENCE 700 1- Cheung A. Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China aut NATIONALLICENCE 773 0- Chromosoma Springer-Verlag 116/6(2007-12-01), 557-568 0009-5915 116:6<557 2007 116 412 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer