@article{bcd3bd8724304c72a140975e9d38dfe8,
title = "A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization",
abstract = "Mre11-Rad50-Xrs2 (MRX) is a highly conserved complex with key roles in various aspects of DNA repair. Here, we report a new function for MRX in limiting transcription in budding yeast. We show that MRX interacts physically and colocalizes on chromatin with the transcriptional co-regulator Mediator. MRX restricts transcription of coding and noncoding DNA by a mechanism that does not require the nuclease activity of Mre11. MRX is required to tether transcriptionally active loci to the nuclear pore complex (NPC), and it also promotes large-scale gene-NPC interactions. Moreover, MRX-mediated chromatin anchoring to the NPC contributes to chromosome folding and helps to control gene expression. Together, these findings indicate that MRX has a role in transcription and chromosome organization that is distinct from its known function in DNA repair.",
keywords = "MRX/N, Mediator, SMC complexes, chromosomal interaction domains, chromosome folding, chromosome organization, coding and non-coding transcription control, nuclear pore",
author = "Romain Forey and Antoine Barthe and Mireille Tittel-Elmer and Maxime Wery and Barrault, {Marie B{\'e}n{\'e}dicte} and C{\'e}cile Ducrot and Andrew Seeber and Nils Krietenstein and Ugo Szachnowski and Magdalena Skrzypczak and Krzysztof Ginalski and Maga Rowicka and Cobb, {Jennifer A.} and Rando, {Oliver J.} and Julie Soutourina and Michel Werner and Karine Dubrana and Gasser, {Susan M.} and Antonin Morillon and Philippe Pasero and Armelle Lengronne and J{\'e}r{\^o}me Poli",
note = "Funding Information: We thank members of the Pasero laboratory and Carol Featherstone for comments on the manuscript. We thank Isma{\"e}l Padioleau and Marc Descrimes for help with bioinformatics. We thank Jason Brickner, Elisa Dultz, Karsten Weis, Katsunori Sugimoto, Vincent G{\'e}li, and Marie-No{\"e}lle Simon for providing strains. We thank the Montpellier Ressources Imagerie (MRI) imaging facility. R.F. was supported by the University of Montpellier . R.F. and J.P. were supported by the Association pour la Recherche contre le Cancer (ARC). Work in the Pasero laboratory is supported by grants from the Agence Nationale de la Recherche (ANR), Institut National Du Cancer (INCa), the Ligue Nationale Contre le Cancer ({\'e}quipe lab{\'e}lis{\'e}e), the Fondation MSDAvenir , and by ARC and ANR (NIRO) grants to A.L. This work has benefited from the facilities and expertise of the NGS platform of Institut Curie, supported by ANR grants ANR-10-EQPX-03 and ANR10-INBS-09-08 (investissements d{\textquoteright}avenir) and by the Canc{\'e}rop{\^o}le {\^I}le-de-France . Work in the Morillon lab was supported by the ANR ( ANR-15-CE12-0007 ) and the ERC (“ EpincRNA ” starting grant and a “ DARK ” consolidator grant). Funding Information: We thank members of the Pasero laboratory and Carol Featherstone for comments on the manuscript. We thank Isma{\"e}l Padioleau and Marc Descrimes for help with bioinformatics. We thank Jason Brickner, Elisa Dultz, Karsten Weis, Katsunori Sugimoto, Vincent G{\'e}li, and Marie-No{\"e}lle Simon for providing strains. We thank the Montpellier Ressources Imagerie (MRI) imaging facility. R.F. was supported by the University of Montpellier. R.F. and J.P. were supported by the Association pour la Recherche contre le Cancer (ARC). Work in the Pasero laboratory is supported by grants from the Agence Nationale de la Recherche (ANR), Institut National Du Cancer (INCa), the Ligue Nationale Contre le Cancer ({\'e}quipe lab{\'e}lis{\'e}e), the Fondation MSDAvenir, and by ARC and ANR (NIRO) grants to A.L. This work has benefited from the facilities and expertise of the NGS platform of Institut Curie, supported by ANR grants ANR-10-EQPX-03 and ANR10-INBS-09-08 (investissements d'avenir) and by the Canc{\'e}rop{\^o}le {\^I}le-de-France. Work in the Morillon lab was supported by the ANR (ANR-15-CE12-0007) and the ERC (“EpincRNA” starting grant and a “DARK” consolidator grant). J.P. A.L. P.P. A.M. M.Wery. M. Werner, S.M.G. J.S. O.J.R. J.C. and K.D. designed the experiments. J.P. A.B. A.L. M.T.-E. M.-B.B. N.K. C.D. and A.S. performed the experiments. M.S. and K.G. did the libraries and sequencing. R.F. U.S. and M.R. did the bioinformatics. Supervision and project administration was done by J.P. and A.L. J.P. wrote the original draft. Writing, review, and editing was done by J.P. A.L. S.M.G. and P.P. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = jan,
day = "7",
doi = "10.1016/j.molcel.2020.11.010",
language = "English (US)",
volume = "81",
pages = "183--197.e6",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",
}