Nrm1 is a bistable switch connecting cell cycle progression to transcriptional control

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• dc.contributor.author Murciano-Julià, Guillem
• dc.contributor.author Vega, Montserrat
• dc.contributor.author Pazo, Esther
• dc.contributor.author Pascual-Serra, Àlex
• dc.contributor.author Alves-Rodrigues, Isabel
• dc.contributor.author Bagudanch, Oriol
• dc.contributor.author Anglada Busquets, Roger
• dc.contributor.author Bonet, Núria
• dc.contributor.author Aligué, Rosa
• dc.contributor.author Moreno, Sergio
• dc.contributor.author Oliva Miguel, Baldomero
• dc.contributor.author Hidalgo Hernando, Elena
• dc.contributor.author Ayté del Olmo, José
• dc.date.accessioned 2025-11-06T17:15:26Z
• dc.date.available 2025-11-06T17:15:26Z
• dc.date.issued 2025
• dc.date.updated 2025-11-06T17:15:26Z
• dc.description.abstract Entry into the cell cycle requires activation of G1 cyclin-dependent kinases (CDKs) and the G1/S transcriptional program. In fission yeast, the MBF complex is the main transcription factor driving early cell-cycle gene expression. MBF-dependent transcription is activated in metaphase and repressed at the end of S phase by a feedback loop involving the cyclin Cig2 and co-repressors Nrm1 and Yox1. While replicative stress inactivates Yox1 via phosphorylation, the mechanism that activates MBF during an unperturbed cell cycle remains unclear. Here, we identify Nrm1 as the key target of cell cycle regulation in a two-step control mechanism. First, CDK1 phosphorylates Nrm1 in metaphase, leading to its release-along with Yox1-from chromatin. Second, unphosphorylated Nrm1, generated either by dephosphorylation or de novo synthesis, is degraded during anaphase, preventing its re-association with MBF until the end of the next S phase. Together, these parallel pathways create a precisely timed window of MBF activation, ensuring proper cell cycle progression and preserving genomic stability.
• dc.description.sponsorship This work was supported by grant PID2022-136449NB-I00 funded by MICIU/AEI/10.13039/501100011033, by Generalitat de Catalunya (Spain) (2021-SGR-00007) and ERDF/EU to JA and by Unidad de Excelencia Maria de Maeztu (CEX2018-000792-M) to JA and EH. EH is a recipient of an ICREA Academia Award (Generalitat de Catalunya). GM-J is a recipient of a FI predoctoral fellowship from Generalitat de Catalunya.
• dc.format.mimetype application/pdf
• dc.identifier.citation Murciano-Julia G, Vega M, Pazo E, Pascual-Serra A, Alves-Rodrigues I, Bagudanch O, Anglada R, Bonet N, Aligue R, Moreno S, Oliva B, Hidalgo E, Ayte J. Nrm1 is a bistable switch connecting cell cycle progression to transcriptional control. EMBO Rep. 2025 Oct;26(20):5048-69. DOI: 10.1038/s44319-025-00566-7
• dc.identifier.doi http://dx.doi.org/10.1038/s44319-025-00566-7
• dc.identifier.issn 1469-221X
• dc.identifier.uri http://hdl.handle.net/10230/71798
• dc.language.iso eng
• dc.publisher EMBO Press
• dc.relation.ispartof EMBO Reports. 2025;26(20):5048-69
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-136449NB-I00
• dc.rights © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword APC/C
• dc.subject.keyword CDK1
• dc.subject.keyword MBF
• dc.subject.keyword Nrm1
• dc.subject.keyword START
• dc.title Nrm1 is a bistable switch connecting cell cycle progression to transcriptional control
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion