The order of PNA-FISH-detected chromosomal telomere lengths in human T-cells is rather stable, even under the influence of strong mutagens.
The nucleo-protein structure of an intact telomere protects each chromosome from being recognized as a break and subsequently being degraded. The DNA component of this structure, the telomeric repeats, undergo attrition with every cell division, as well as in response to endogenous events, like oxidative stress. Exposure to exogenous damage promotes this process and leads to growth arrest, apoptosis and eventually to malignant transformation. It was thought that the shortest chromosome ends in humans are the most susceptible ones to become dysfunctional telomeres, and have therefore an important role in cell death and cancer. Here, we show that a stable hierarchy exists in the form of a telomere length profile of the whole human karyotype. This rank order is conserved between different human cell types and individuals, is maintained throughout a lifetime, and seems to be genetically determined. As a particular feature, this telomere length profile differs only marginally when normal human cell cultures and malignant transformed cells are compared. The profile is moreover stable when these different human cells are exposed to mutagens such as bleomycin or mitomycin C. From these findings, the question arises if also the stably long telomeres have a basic biological function.
Wick
U
U
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
Gebhart
E
E
D001761:Bleomycin / Q000633:toxicity; D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000187:drug effects / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015459:Leukemia-Lymphoma, Adult T-Cell; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D015341:Nucleic Acid Probes; D009698:Nucleoproteins / Q000378:metabolism; D020135:Peptide Nucleic Acids / Q000737:chemistry; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects; D016615:Telomere / Q000187:drug effects* / Q000235:genetics
D009153:Mutagens; D015341:Nucleic Acid Probes; D009698:Nucleoproteins; D020135:Peptide Nucleic Acids; D001761:Bleomycin; D016685:Mitomycin