The three-dimensional organization of telomeres in the nucleus of mammalian cells
- Equal contributors
1 Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB, R3E 0V9, Canada
2 German Cancer Research Centre, Division of Genetics of Skin Carcinogenesis, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
3 Department of Otolaryngology Head and Neck Surgery, Health Sciences Centre, GB421-820 Sherbrook Street, Winnipeg MB, R3A 1R9, Canada
4 Delft University of Technology, Faculty of Applied Sciences, Department of Imaging Science & Technology, 2628 CJ Delft, The Netherlands
5 Hematology Department, IETG Laboratory, University Hospital Jean Minjoz, 25030 Besançon, France
6 Present address: Hematology Laboratory, University Hospital Pontchaillou, 35033 Rennes, France
BMC Biology 2004, 2:12 doi:10.1186/1741-7007-2-12Published: 3 June 2004
The observation of multiple genetic markers in situ by optical microscopy and their relevance to the study of three-dimensional (3D) chromosomal organization in the nucleus have been greatly developed in the last decade. These methods are important in cancer research because cancer is characterized by multiple alterations that affect the modulation of gene expression and the stability of the genome. It is, therefore, essential to analyze the 3D genome organization of the interphase nucleus in both normal and cancer cells.
We describe a novel approach to study the distribution of all telomeres inside the nucleus of mammalian cells throughout the cell cycle. It is based on 3D telomere fluorescence in situ hybridization followed by quantitative analysis that determines the telomeres' distribution in the nucleus throughout the cell cycle. This method enables us to determine, for the first time, that telomere organization is cell-cycle dependent, with assembly of telomeres into a telomeric disk in the G2 phase. In tumor cells, the 3D telomere organization is distorted and aggregates are formed.
The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability. Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases. Such new avenues of monitoring genomic instability could potentially impact on cancer biology, genetics, diagnostic innovations and surveillance of treatment response in medicine.