Séminaire Département de Biologie - Dr Julie SOUTOURINA
le 19 Mai 2016 à 11h en Amphithéâtre Grégory
Dr. Julie SOUTOURINA, Institute for Integrative Biology of the Cell (I2BC), Institute of Biology and Technologies – Saclay (iBiTec-S),
CEA - CNRS - Université Paris-Sud – Université Paris-Saclay, F-91191 Gif-sur-Yvette cedex
Molecular mechanisms of Mediator functions in transcription and DNA repair
Mediator complex is crucial for transcription regulation in all eukaryotes and mutations in human Mediator are implicated in developmental diseases and cancer. Despite intensive research, the mechanisms of its in vivo action remain to be elucidated. Previously, our in vivo studies of the yeast Saccharomyces cerevisiae Mediator complex demonstrated a functional interplay between Mediator and components of the transcription machinery including RNA polymerase II1. Applying integrative approaches, we aim to enhance our understanding of the key Mediator mechanisms in transcription regulation and to uncover the rules that determine the preinitiation complex (PIC) assembly at the genome level. We are investigating the role of essential Mediator subunits in transcription regulation using in vivo, in vitro and in silico approaches2.
Transcription is coupled with DNA repair. Maintenance of genome integrity and transcription are two key functions of the cell, allowing the transmission and expression of the genetic material. How these processes are coordinated in vivo in eukaryotes remains a key biological question that relates to serious human diseases. Recently, we have discovered a novel role of Mediator as a link between transcription and DNA repair via a direct contact with Rad2 endonuclease, the yeast homolog of human XPG protein, a key component of nucleotide excision DNA repair3. Our results suggest that Mediator is involved in transcription-coupled DNA repair by facilitating Rad2/XPG recruitment to transcribed genes. We are now addressing the molecular mechanisms governing the Mediator link with DNA repair machinery and the question of the conservation of these mechanisms in human cells. We propose that Mediator complex might play more roles in nuclear processes than previously assumed4.
1. J. Soutourina, S. Wydau, Y. Ambroise, C. Boschiero, M. Werner, Direct interaction of RNA polymerase II and mediator required for transcription in vivo. Science 331, 1451 (2011).
2. F. Eyboulet, S. Wydau-Dematteis, T. Eychenne, O. Alibert, H. Neil, C. Boschiero, M.-C. Nevers, H. Volland, D. Cornu, V. Redeker, M. Werner, & J. Soutourina. Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo. Nucleic Acids Research, 43, 9214-9231 (2015).
3. F. Eyboulet, C. Cibot, T. Eychenne, H. Neil, O. Alibert, M. Werner & J. Soutourina, Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment. Genes Dev 27, 2549-2562 (2013).
4. .J. Soutourina, M. Werner, A novel link of Mediator with DNA repair. Cell Cycle 13, 1362-1363 (2014).
Lieu(x) : Ecole Polytechnique, Amphithéâtre Grégory
Contact : Emmanuelle Schmitt (emmanuelle.schmitt at polytechnique.edu)