A three-year PhD position starting in October 2014 and financed by the CEA is available in the Genome transcriptional expression group of the Institute of Biology and Technology Saclay, CEA/Saclay (Paris region, France). Highly motivated candidates will be selected by a competitive PhD recruitment process, named Irtelis. Applications must be made on the Irtelis website (on-line application deadline for the CEA International PhD program in Life Sciences: Friday, March 21, 2014, http://www-dsv.cea.fr/en/phd-program).
PhD project summary
In eukaryotes, transcription as a first step of gene expression is tightly regulated and many multiprotein complexes are implicated in this essential process. Mediator of transcription regulation is one of these complexes conserved in all eukaryotes. Mediator is responsible for the recruitment of RNA polymerase II to promoters in response to transcription activators. The crucial role of Mediator in transcription activation is now largely accepted. However, we found that this complex also plays an important role by connecting transcription and DNA repair via a direct contact with Rad2/XPG DNA repair protein. Mutations in human XPG gene give rise to a xeroderma pigmentosum (XP) sometimes associated with Cockayne syndrome (CS). In this project, we propose to study, in vivo, the molecular mechanisms of Mediator function as a link between transcription and DNA repair. We will use the budding yeast and human cells as our models, addressing the conservation of the mechanisms in eukaryotes, and applying integrative approaches spanning advanced functional genomics, molecular biology, genetics, biochemistry, and bioinformatics. In conclusion, we aim to decipher a new Mediator role in DNA repair shedding light on the functional interplay between transcription and DNA repair, two fundamental processes, dysfunctions of which lead to serious human diseases.
Eyboulet F., Cibot C., Eychenne T., Neil H., Alibert O., Werner M., & Soutourina J. (2013) Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment. Genes & Dev. 27, 2549-2562.
Soutourina J., Wydau S., Ambroise Y., Boschiero C., & Werner M. (2011) Direct Interaction of RNA Polymerase II and Mediator Required for Transcription in Vivo. Science, 331, 1451-1454.
Esnault C., Ghavi-Helm Y., Brun S., Soutourina J., van Berkum N., Holstege F. & Werner M. (2008). Mediator-dependent recruitment of TFIIH modules in preinitiation complex. Mol. Cell 31, 337-346.
Dr. Julie Soutourina
Phone: +33 (0)1 69 08 54 13
CEA/Saclay, SBIGeM, Bât. 144
91191 Gif-sur-Yvette Cedex France
Commissariat à l’énergie atomique et aux énergies alternatives
Centre de Saclay ⏐ 91191 Gif-sur-Yvette Cedex
T. +33 (0)1 69 08 54 13 ⏐ F. +33 (0)1 69 08 47 12
Etablissement public à caractère industriel et commercial ⏐RCS Paris B 775 685 019
Direction des Science du Vivant
Institut de Biologie et Technologies – Saclay
Service de Biologie Intégrative et Génétique Moléculaire