Telomeres, the natural ends of linear chromosomes, protect our genetic material from degradation and our chromosomes from fusion. They consist of tandem TTAGGG repeats and their status are regulated by the Shelterin protein complex that controls telomere length and telomere integrity. Interestingly, telomeres have an essential function in the organization of the nucleus in a variety of organisms. The interphase nucleus is highly compartmentalized, and during the last decades it has become clear that chromosomes occupy specific discrete territories. This spatial organization of the genome has emerged as an essential aspect of gene regulation and genome stability, and the function of human telomeres in this process is still elusive.

The Crabbe lab is studying telomere dynamics in human primary and cancer cells, using specific tools that allow the visualization of telomeres in live cells by confocal and super-resolution microscopy.

We reported for the first time in human cells that telomeres are tethered to the nuclear envelope during postmitotic nuclear assembly (Crabbe et al., 2012). Imaging techniques are also used to follow other aspects of telomere dynamics such as the formation of clusters and telomere diffusion rate.


We are also using biochemistry and proteomics to characterize the mechanism of telomere tethering to the nuclear envelope. We already know that RAP1, a telomeric protein member of the Shelterin complex, can interact with SUN1, a protein from the nuclear envelope. One of our goal is to determine whether other interactions between proteins from the telomeres and proteins from the nuclear envelope are taking place, and understand their function on the formation of the nuclear envelope after mitosis, on chromosome organization in the nucleus, and also on telomere maintenance.

The lab is also studying telomere dynamics in the context of chronological or premature aging. In human somatic cells, the replication-dependent loss of telomeric repeats is not compensated by telomerase, the enzyme able to elongate telomeres, leading to a progressive telomere shortening. How this shortening affects telomere dynamics is under investigation. The protective nature of telomeres can be challenged when the nucleoprotein cap is dysfunctional. When telomeres are unmasked, they elicit a DNA damage reponse (DDR) that can be visualized by the recruitment of checkpoint proteins at chromosome ends. We generated tools to visualize the accumulation of DDR markers in live cells. This now allows us to specifically follow unprotected telomeres and study their dynamic in the nucleus.

Key words

Telomeres, genome organization, nuclear envelope, aging, cancer, shelterin, DNA damage checkpoint

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The Crabbe lab is located at the Center for Integrative Biology (CBI) in the beautiful city of Toulouse (South of France). The CBI currently brings together more than 400 scientists that foster research leading to the elucidation of fundamental aspects of the structure and function of complex biological systems, and ranging from individual molecules to the whole organism and population. Within a highly-collaborative scientific environment, researchers have access to either in-house or nearby state-of-the art technological facilities, including photonic and electron microscopy, a computer cluster for large data analysis and simulation, animal facilities, deep sequencing and proteomics.



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