Telomeres and Genome Organization

Presentation

The Crabbe lab is interested in studying the role of telomere dynamics in the nuclear organization of human cells. We focus on the interactions between telomeres and the nuclear envelope during the cell cycle, and study the impact of telomere distribution on genome stability, nuclear organization, gene expression, DNA repair and cell growth.

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 focused on:

1. The mechanisms driving telomere and nuclear envelope interaction that occurs during post-mitotic nuclear assembly (Crabbe et al, Cell Reports 2012)
2. The identification of tethered telomeres/chromosomes and whether they are conserved throughout cell division
3. How telomere-nuclear envelope interaction during nuclear reformation can affect chromosome organization
4. The role of telomeres in the reformation of the nuclear envelope during late anaphase
5. Impact of nuclear envelope dysfunction on telomere homeostasis and aging  

We are using a wide range of techniques from basic cellular and molecular biology, biochemistry, advanced microscopy on fixed and live cells. We also developed MadID, a new technique to map protein-DNA interaction (Sobecki et al, Cell Reports 2018).

Publications

• Masamsetti, V.P., Low, R.R.J., Mak, K.S., O'Connor, A., Riffkin, C.D., Lamm, N., Crabbe, L., Karlseder, J., Huang, D.C.S., Hayashi, M.T., Cesare, A.J.
  Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection
  Nature Communication
  2019 Sep
• Michal Sobecki, Charbel Souaid, Jocelyne Boulay, Vincent Guerineau, Daan Noordermeer, and Laure Crabbe.
  MadID, a Versatile Approach to Map Protein-DNA Interactions, Highlights Telomere-Nuclear Envelope Contact Sites in Human Cells
  Cell Reports
  2018 Dec
• Pardo, B., Crabbe, L., and Pasero, P..
  Signaling Pathways of Replication Stress in Yeast
  FEMS Yeast Res.
  2017 Mar
• Sobilo, L., Kurfürst, R., Loubens, V., Martin, M., Mondon, P., Jeanneton, O., Heusèle, C., Ossant, F., Lespessailles, E., Toumi, H., Crabbe, L., and Schnebert, S.
  Impact of exogenous stress on TGF-β inducible early gene 1 in human skin cells
  Experimental Dermatology
  2015 Nov
• Cesare, A.J., Hayashi, M.T., Crabbe, L., and Karlseder, J.
  The telomere deprotection response is functionally distinct from the genomic DNA damage response
  Molecular Cell
  2013 Jul

Funding

       

Alumni

Ganna Kychygina

Alexandre Bouniot, Ingénieur EVOTEC

Michal Sobecki, postdoc at University of Zurich (UZH)