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Título: | The replication checkpoint protects fork stability by releasing transcribed genes from nuclear pores |
Autor: | Bermejo, Rodrigo CSIC ORCID CVN ; Gómez-González, Belén CSIC ORCID; Aguilera, Andrés CSIC ORCID; Foiani, Marco | Palabras clave: | Cell cycle proteins Hydroxyurea RAD53 protein Threonine kinases |
Fecha de publicación: | 22-jul-2011 | Editor: | Elsevier | Citación: | Cell 146(2): 233-246 (2011) | Resumen: | Transcription hinders replication fork progression and stability, and the Mec1/ATR checkpoint protects fork integrity. Examining checkpoint-dependent mechanisms controlling fork stability, we find that fork reversal and dormant origin firing due to checkpoint defects are rescued in checkpoint mutants lacking THO, TREX-2, or inner-basket nucleoporins. Gene gating tethers transcribed genes to the nuclear periphery and is counteracted by checkpoint kinases through phosphorylation of nucleoporins such as Mlp1. Checkpoint mutants fail to detach transcribed genes from nuclear pores, thus generating topological impediments for incoming forks. Releasing this topological complexity by introducing a double-strand break between a fork and a transcribed unit prevents fork collapse. Mlp1 mutants mimicking constitutive checkpoint-dependent phosphorylation also alleviate checkpoint defects. We propose that the checkpoint assists fork progression and stability at transcribed genes by phosphorylating key nucleoporins and counteracting gene gating, thus neutralizing the topological tension generated at nuclear pore gated genes. | Descripción: | Under a Creative Commons license.-- et al. | Versión del editor: | http://dx.doi.org/10.1016/j.cell.2011.06.033 | URI: | http://hdl.handle.net/10261/52330 | DOI: | 10.1016/j.cell.2011.06.033 | Identificadores: | issn: 0092-8674 |
Aparece en las colecciones: | (CABIMER) Artículos |
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Nuclear Pores.pdf | 2,39 MB | Adobe PDF | Visualizar/Abrir |
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