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 PaseroArmelle Lengronne, Jérôme Poli

Biochemistry & Molecular Biology

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

1 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

AU - Ducrot, Cécile

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AU - Krietenstein, Nils

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AU - Skrzypczak, Magdalena

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AU - Cobb, Jennifer A.

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AU - Soutourina, Julie

AU - Werner, Michel

AU - Dubrana, Karine

AU - Gasser, Susan M.

AU - Morillon, Antonin

AU - Pasero, Philippe

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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