Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment (original) (raw)

  1. Camille Cibot1,2,3,5,
  2. Thomas Eychenne1,2,3,
  3. Helen Neil1,2,3,6,
  4. Olivier Alibert4,
  5. Michel Werner1,2,3 and
  6. Julie Soutourina1,2,3,7
  7. 1FRE3377, Institut de Biologie et de Technologies de Saclay (iBiTec-S), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), F-91191 Gif-sur-Yvette cedex, France;
  8. 2FRE3377, Centre National de la Recherche Scientifique (CNRS), F-91191 Gif-sur-Yvette Cedex, France;
  9. 3FRE3377, Université Paris-Sud, F-91191 Gif-sur-Yvette Cedex, France;
  10. 4Institut de Radiobiologie Cellulaire et Moléculaire (iRCM), CEA, F-91057 Evry Cedex, France

Abstract

Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with DNA repair. We identified a functional contact between the Med17 Mediator subunit and Rad2/XPG, the 3′ endonuclease involved in nucleotide excision DNA repair. Genome-wide location analyses revealed that Rad2 is associated with RNA polymerase II (Pol II)- and Pol III-transcribed genes and telomeric regions in the absence of exogenous genotoxic stress. Rad2 occupancy of Pol II-transcribed genes is transcription-dependent. Genome-wide Rad2 occupancy of class II gene promoters is well correlated with that of Mediator. Furthermore, UV sensitivity of med17 mutants is correlated with reduced Rad2 occupancy of class II genes and concomitant decrease of Mediator interaction with Rad2 protein. Our results suggest that Mediator is involved in DNA repair by facilitating Rad2 recruitment to transcribed genes.

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