Tilman, Gaëlle
[UCL]
Loriot, Axelle
[UCL]
Van Beneden, Amandine
[UCL]
Arnoult, Nausica
[UCL]
Londono-Vallejo, Arturo
[UCL]
De Smet, Charles
[UCL]
Decottignies, Anabelle
[UCL]
Telomeres are specialized structures that cap the ends of chromosomes. Mammalian telomeres and subtelomeres display epigenetic features characteristic of heterochromatin. We are investigating whether epigenetic marks of chromosome ends affect telomere maintenance and, conversely, whether telomere maintenance mechanisms, especially in the context of tumor cells, impact on these epigenetic features. Tumor cells rely either on telomerase or on an alternative mechanism (ALT) for telomere maintenance. Mechanisms of ALT activation are still poorly understood, but recent studies suggested that DNA hypomethylation of chromosome ends might contribute to the process by facilitating telomeric sister chromatid exchanges (T-SCEs). We found that ALT/T-SCEhigh tumor cells display low subtelomeric DNA methylation levels. Surprisingly however, the same sequences retained high methylation levels in ALT/T-SCEhigh SV40-immortalized fibroblasts, suggesting that, while subtelomeric DNA hypomethylation is often coincident with the ALT process in tumor cells, it is not required for T-SCE. This led us to investigate the process of genomic DNA demethylation during the tumorigenesis. It is currently believed that demethylation of genomic DNA is an early event in the tumorigenic process that is probably triggering chromosomal instability. How DNA demethylation occurs is still an open question and it remains to be established whether all regions of the genome are subjected to equal demethylation. The “Chromatin and Cancer” symposium held in Cambridge shed light on the connection between heterochromatin, DNA damage and DNA repair. We believe that this may help understanding how DNA demethylation occurs. Clues to unravel the mechanisms of tumorigenesis-driven hypermethylation of certain regions of the genome may also emerge from this.
Bibliographic reference |
Tilman, Gaëlle ; Loriot, Axelle ; Van Beneden, Amandine ; Arnoult, Nausica ; Londono-Vallejo, Arturo ; et. al. Subtelomeric DNA hypomethylation is not required for telomeric sister chromatid exchanges in ALT cells.Chromatin and Cancer (Cambridge (UK) , du 06/07/2009 au 09/07/2009). |
Permanent URL |
http://hdl.handle.net/2078.1/137027 |