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The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51 (+) Gene in Response to DNA Replication Stress
DNA replication stress induces the transcriptional activation of rhp51 (+), a fission yeast recA homolog required for repair of DNA double strand breaks. However, the mechanism by which DNA replication stress activates rhp51 (+) transcription is not understood. The promoter region of rhp51 (+) conta...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221157/ https://www.ncbi.nlm.nih.gov/pubmed/25372384 http://dx.doi.org/10.1371/journal.pone.0111936 |
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author | Sartagul, Wugangerile Zhou, Xin Yamada, Yuki Ma, Ning Tanaka, Katsunori Furuyashiki, Tomoyuki Ma, Yan |
author_facet | Sartagul, Wugangerile Zhou, Xin Yamada, Yuki Ma, Ning Tanaka, Katsunori Furuyashiki, Tomoyuki Ma, Yan |
author_sort | Sartagul, Wugangerile |
collection | PubMed |
description | DNA replication stress induces the transcriptional activation of rhp51 (+), a fission yeast recA homolog required for repair of DNA double strand breaks. However, the mechanism by which DNA replication stress activates rhp51 (+) transcription is not understood. The promoter region of rhp51 (+) contains two damage-responsive elements (DREs) and two MluI cell cycle box (MCB) motifs. Using luciferase reporter assays, we examined the role of these elements in rhp51 (+) transcription. The full-length rhp51 (+) promoter and a promoter fragment containing MCB motifs only, but not a fragment containing DREs, mediated transcriptional activation upon DNA replication stress. Removal of the MCB motifs from the rhp51 (+) promoter abolished the induction of rhp51 (+) transcription by DNA replication stress. Consistent with a role for MCB motifs in rhp51 (+) transcription activation, deletion of the MBF (MCB-binding factor) co-repressors Nrm1 and Yox1 precluded rhp51 (+) transcriptional induction in response to DNA replication stress. Using cells deficient in checkpoint signaling molecules, we found that the Rad3-Cds1/Chk1 pathway partially mediated rhp51 (+) transcription in response to DNA replication stress, suggesting the involvement of unidentified checkpoint signaling pathways. Because MBF is critical for G1/S transcription, we examined how the cell cycle affected rhp51 (+) transcription. The transcription of rhp51 (+) and cdc18 (+), an MBF-dependent G1/S gene, peaked simultaneously in synchronized cdc25-22 cells. Furthermore, DNA replication stress maintained transcription of rhp51 (+) similarly to cdc18 (+). Collectively, these results suggest that MBF and its regulators mediate rhp51 (+) transcription in response to DNA replication stress, and underlie rhp51 (+) transcription at the G1/S transition. |
format | Online Article Text |
id | pubmed-4221157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42211572014-11-12 The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51 (+) Gene in Response to DNA Replication Stress Sartagul, Wugangerile Zhou, Xin Yamada, Yuki Ma, Ning Tanaka, Katsunori Furuyashiki, Tomoyuki Ma, Yan PLoS One Research Article DNA replication stress induces the transcriptional activation of rhp51 (+), a fission yeast recA homolog required for repair of DNA double strand breaks. However, the mechanism by which DNA replication stress activates rhp51 (+) transcription is not understood. The promoter region of rhp51 (+) contains two damage-responsive elements (DREs) and two MluI cell cycle box (MCB) motifs. Using luciferase reporter assays, we examined the role of these elements in rhp51 (+) transcription. The full-length rhp51 (+) promoter and a promoter fragment containing MCB motifs only, but not a fragment containing DREs, mediated transcriptional activation upon DNA replication stress. Removal of the MCB motifs from the rhp51 (+) promoter abolished the induction of rhp51 (+) transcription by DNA replication stress. Consistent with a role for MCB motifs in rhp51 (+) transcription activation, deletion of the MBF (MCB-binding factor) co-repressors Nrm1 and Yox1 precluded rhp51 (+) transcriptional induction in response to DNA replication stress. Using cells deficient in checkpoint signaling molecules, we found that the Rad3-Cds1/Chk1 pathway partially mediated rhp51 (+) transcription in response to DNA replication stress, suggesting the involvement of unidentified checkpoint signaling pathways. Because MBF is critical for G1/S transcription, we examined how the cell cycle affected rhp51 (+) transcription. The transcription of rhp51 (+) and cdc18 (+), an MBF-dependent G1/S gene, peaked simultaneously in synchronized cdc25-22 cells. Furthermore, DNA replication stress maintained transcription of rhp51 (+) similarly to cdc18 (+). Collectively, these results suggest that MBF and its regulators mediate rhp51 (+) transcription in response to DNA replication stress, and underlie rhp51 (+) transcription at the G1/S transition. Public Library of Science 2014-11-05 /pmc/articles/PMC4221157/ /pubmed/25372384 http://dx.doi.org/10.1371/journal.pone.0111936 Text en © 2014 Sartagul et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sartagul, Wugangerile Zhou, Xin Yamada, Yuki Ma, Ning Tanaka, Katsunori Furuyashiki, Tomoyuki Ma, Yan The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51 (+) Gene in Response to DNA Replication Stress |
title | The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51
(+) Gene in Response to DNA Replication Stress |
title_full | The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51
(+) Gene in Response to DNA Replication Stress |
title_fullStr | The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51
(+) Gene in Response to DNA Replication Stress |
title_full_unstemmed | The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51
(+) Gene in Response to DNA Replication Stress |
title_short | The MluI Cell Cycle Box (MCB) Motifs, but Not Damage-Responsive Elements (DREs), Are Responsible for the Transcriptional Induction of the rhp51
(+) Gene in Response to DNA Replication Stress |
title_sort | mlui cell cycle box (mcb) motifs, but not damage-responsive elements (dres), are responsible for the transcriptional induction of the rhp51
(+) gene in response to dna replication stress |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221157/ https://www.ncbi.nlm.nih.gov/pubmed/25372384 http://dx.doi.org/10.1371/journal.pone.0111936 |
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