Séminaire Département de Biologie - Dr. Marie- Hélène Le Du

le 06 Juin 2016 à 11h en Amphithéâtre Grégrory

Dr. Marie-Hélène Le Du, Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS,
Université Paris-Sud,  Batiment 144, CEA Saclay,Gif-sur-Yvette, F-91191, France.

Functional and structural plasticity at telomeres

Telomeres are nucleoprotein complexes that protect the extremities of linear chromosomes from degradation or illicit repair. At each cell division, telomeres shorten due to incomplete end replication until they reach a critical length at which cells enter senescence.

One major aspect of telomere architecture comes from the DNA telomere repeats observed in all eukaryotic species, which induces subnuclear compartment with high local concentration of telomere proteins. This elevated local concentration implies that the description of high affinity interactions is not sufficient to properly understand the regulatory processes involved in telomere maintenance. It is known that weak-affinity (KD > 10-4 M) and transient interactions are equally important than high-affinity interactions (KD < 10-6 M) in the regulation of many cellular pathways. In telomeres biology, shortening is a crucial issue with different functions associated to short versus long telomere states, which also induces variation of local concentrations that may therefore be linked to critical functional switches. However, the available technical tools to study short-lived interactions limit our understanding of these regulatory processes. Weak and transient interactions are particularly difficult to study in multifunctional proteins, which interact with numerous partners often through a common or similar interface.

The protein Rap1 is the only telomeric protein found physically and functionally associated to telomere from yeast to human. In the yeast Saccharomyces cerevisiae it directly binds telomeric DNA and plays a central role, in Human it is recruited through its interaction with the protein TRF2 and its telomeric function remains controversial.

Rap1 structure includes three globular domains connected by flexible unstructured regions. Its interaction with DNA in yeast or with TRF2 in Human is associated with large conformational adjustment. Our extensive studies of Rap1 proteins reveal an essential conserved structural plasticity. This plasticity allows the formation of different entities with its various partners, which are sensitive to local concentrations and therefore to telomere state.

- Gaullier G et al., Nucleic Acids Research, 2016.
- Benarroch-Popivker D et al..  Mol Cell, 2016.
- Giraud-Panis M-J et al. Front. Oncol., 2013.
- Le Bihan Y-V et al. Acta Cryst D., 2013.
- Poulet A  et al. Nucleic Acids Research, 2012.
- Matot B et al. Nucleic Acids Research, 2012.

Lieu(x) :  Ecole Polytechnique, Amphithéâtre Grégory

Contact : Emmanuelle Schmitt (emmanuelle.schmitt at polytechnique.edu)