A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization

Romain Forey; Antoine Barthe; Mireille Tittel-Elmer; Maxime Wery; Marie Bénédicte Barrault; Cécile Ducrot; Andrew Seeber; Nils Krietenstein; Ugo Szachnowski; Magdalena Skrzypczak; Krzysztof Ginalski; Maga Rowicka; Jennifer A. Cobb; Oliver J. Rando; Julie Soutourina; Michel Werner; Karine Dubrana; Susan M. Gasser; Antonin Morillon; Philippe Pasero; Armelle Lengronne; Jérôme Poli

doi:10.1016/j.molcel.2020.11.010

A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization

Romain Forey
, Antoine Barthe
, Mireille Tittel-Elmer
, Maxime Wery
, Marie Bénédicte Barrault
, Cécile Ducrot
, Andrew Seeber
, Nils Krietenstein
, Ugo Szachnowski
, Magdalena Skrzypczak
, Krzysztof Ginalski
, Maga Rowicka
, Jennifer A. Cobb
, Oliver J. Rando
, Julie Soutourina
, Michel Werner
, Karine Dubrana
, Susan M. Gasser
, Antonin Morillon
, Philippe Pasero

Armelle Lengronne, Jérôme Poli

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Pages (from-to)	183-197.e6
Journal	Molecular cell
Volume	81
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2020.11.010
State	Published - Jan 7 2021

Keywords

MRX/N
Mediator
SMC complexes
chromosomal interaction domains
chromosome folding
chromosome organization
coding and non-coding transcription control
nuclear pore

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2020.11.010

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Forey, R., Barthe, A., Tittel-Elmer, M., Wery, M., Barrault, M. B., Ducrot, C., Seeber, A., Krietenstein, N., Szachnowski, U., Skrzypczak, M., Ginalski, K., Rowicka, M., Cobb, J. A., Rando, O. J., Soutourina, J., Werner, M., Dubrana, K., Gasser, S. M., Morillon, A., ... Poli, J. (2021). A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization. Molecular cell, 81(1), 183-197.e6. https://doi.org/10.1016/j.molcel.2020.11.010

Forey, R, Barthe, A, Tittel-Elmer, M, Wery, M, Barrault, MB, Ducrot, C, Seeber, A, Krietenstein, N, Szachnowski, U, Skrzypczak, M, Ginalski, K, Rowicka, M, Cobb, JA, Rando, OJ, Soutourina, J, Werner, M, Dubrana, K, Gasser, SM, Morillon, A, Pasero, P, Lengronne, A & Poli, J 2021, 'A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization', Molecular cell, vol. 81, no. 1, pp. 183-197.e6. https://doi.org/10.1016/j.molcel.2020.11.010

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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.",

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AU - Barrault, Marie Bénédicte

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AU - Werner, Michel

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AU - Gasser, Susan M.

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AU - Lengronne, Armelle

AU - Poli, Jérôme

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A Role for the Mre11-Rad50-Xrs2 Complex in Gene Expression and Chromosome Organization

Abstract

Keywords

ASJC Scopus subject areas

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