Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active.
<h4>Background</h4>In fission yeast Schizosaccharomyces pombe G1/S cell-cycle regulated transcription depends upon MBF. A negative feedback loop involving Nrm1p and Yox1p bound to MBF leads to transcriptional repression as cells exit G1 phase. However, activation of the DNA replication c...
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Public Library of Science (PLoS)
2011-02-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017211&type=printable |
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| author | Catia Caetano Steffi Klier Robertus A M de Bruin |
| author_facet | Catia Caetano Steffi Klier Robertus A M de Bruin |
| author_sort | Catia Caetano |
| collection | DOAJ |
| description | <h4>Background</h4>In fission yeast Schizosaccharomyces pombe G1/S cell-cycle regulated transcription depends upon MBF. A negative feedback loop involving Nrm1p and Yox1p bound to MBF leads to transcriptional repression as cells exit G1 phase. However, activation of the DNA replication checkpoint response during S phase results in persistent expression of MBF-dependent genes.<h4>Methodology/principal findings</h4>This report shows that Yox1p binding to MBF is Nrm1-dependent and that Yox1p and Nrm1p require each other to bind and repress MBF targets. In response to DNA replication stress both Yox1p and Nrm1p dissociate from MBF at promoters leading to de-repression of MBF targets. Inactivation of Yox1p is an essential part of the checkpoint response. Cds1p (human Chk2p) checkpoint protein kinase-dependent phosphorylation of Yox1p promotes its dissociation from the MBF transcription factor. We establish that phosphorylation of Yox1p at Ser114, Thr115 is required for maximal checkpoint-dependent activation of the G1/S cell-cycle transcriptional program.<h4>Conclusions/significance</h4>This study shows that checkpoint-dependent phosphorylation of Yox1p at Ser114, Thr115 results in de-repression of the MBF transcriptional program. The remodeling of the cell cycle transcriptional program by the DNA replication checkpoint is likely to comprise an important mechanism for the avoidance of genomic instability. |
| format | Article |
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| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-02-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-e5c6b5ea12224f809e66e4fc21a09b132025-08-20T02:09:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-02-0162e1721110.1371/journal.pone.0017211Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active.Catia CaetanoSteffi KlierRobertus A M de Bruin<h4>Background</h4>In fission yeast Schizosaccharomyces pombe G1/S cell-cycle regulated transcription depends upon MBF. A negative feedback loop involving Nrm1p and Yox1p bound to MBF leads to transcriptional repression as cells exit G1 phase. However, activation of the DNA replication checkpoint response during S phase results in persistent expression of MBF-dependent genes.<h4>Methodology/principal findings</h4>This report shows that Yox1p binding to MBF is Nrm1-dependent and that Yox1p and Nrm1p require each other to bind and repress MBF targets. In response to DNA replication stress both Yox1p and Nrm1p dissociate from MBF at promoters leading to de-repression of MBF targets. Inactivation of Yox1p is an essential part of the checkpoint response. Cds1p (human Chk2p) checkpoint protein kinase-dependent phosphorylation of Yox1p promotes its dissociation from the MBF transcription factor. We establish that phosphorylation of Yox1p at Ser114, Thr115 is required for maximal checkpoint-dependent activation of the G1/S cell-cycle transcriptional program.<h4>Conclusions/significance</h4>This study shows that checkpoint-dependent phosphorylation of Yox1p at Ser114, Thr115 results in de-repression of the MBF transcriptional program. The remodeling of the cell cycle transcriptional program by the DNA replication checkpoint is likely to comprise an important mechanism for the avoidance of genomic instability.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017211&type=printable |
| spellingShingle | Catia Caetano Steffi Klier Robertus A M de Bruin Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active. PLoS ONE |
| title | Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active. |
| title_full | Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active. |
| title_fullStr | Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active. |
| title_full_unstemmed | Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active. |
| title_short | Phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keeps the G1/S cell-cycle transcriptional program active. |
| title_sort | phosphorylation of the mbf repressor yox1p by the dna replication checkpoint keeps the g1 s cell cycle transcriptional program active |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017211&type=printable |
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