A homeodomain transcription factor regulates the DNA replication checkpoint in yeast

Purtill, Frances S.; Whitehall, Simon K.; Williams, Emma S.; McInerny, Christopher; Sharrocks, Andrew D.; Morgan, Brian A.

doi:10.4161/cc.10.4.14824

Cited by 14 publications

(11 citation statements)

References 32 publications

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“…However, in addition to Nrm1, the transcriptional repressor Yox1 is also required to confine transcription to the G1 phase (Aligianni et al , 2009). It has been shown that in response to replication stress, MBF‐dependent transcription is activated via checkpoint protein kinase Cds1 phosphorylation‐dependent inactivation of both Nrm1 and Yox1 (de Bruin et al , 2008; Caetano et al , 2011; Gomez‐Escoda et al , 2011; Purtill et al , 2011). Overall, our study shows that the mechanism that governs the remodelling of the cell‐cycle transcriptional programme by the DNA replication checkpoint is conserved between these distantly related yeasts.…”

Section: Discussionmentioning

confidence: 99%

Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1/S genes

et al. 2012

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Reprogramming gene expression is crucial for DNA replication stress response. We used quantitative proteomics to establish how the transcriptional response results in changes in protein levels. We found that expression of G1/S cell-cycle targets are strongly up-regulated upon replication stress, and show that MBF, but not SBF genes, are up-regulated via Rad53-dependent inactivation of the MBF co-repressor Nrm1. A subset of G1/S genes was found to undergo an SBF-to-MBF switch at the G1/S transition, enabling replication stress-induced transcription of genes targeted by SBF during G1. This subset of G1/S genes is characterized by an overlapping Swi4/ Mbp1-binding site and is enriched for genes that cause a cell cycle and/or growth defect when overexpressed. Analysis of the prototypical switch gene TOS4 (Target Of SBF 4) reveals its role as a checkpoint effector supporting the importance of this distinct class of G1/S genes for the DNA replication checkpoint response. Our results reveal that replication stress induces expression of G1/S genes via the Rad53-MBF pathway and that an SBF-to-MBF switch characterizes a new class of genes that can be induced by replication stress.

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Section: Discussionmentioning

confidence: 99%

Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1/S genes

et al. 2012

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“…Activation of these MBF-responsive genes results from checkpoint signalling-dependent inhibition of the negative feedback loop that turns off G1–S transcription during G1-to-S phase transition. The checkpoint effector kinases Rad53 and Cds1 directly target and inhibit the main G1–S transcriptional co-repressor Nrm1 in budding yeast and Nrm1 and Yox1 in fission yeast 101,102,110–114 (FIG. 3).…”

Section: G1–s Transcription and Genome Stabilitymentioning

confidence: 99%

Control of cell cycle transcription during G1 and S phases

Bertoli

Skotheim

Bruin

2013

Nat Rev Mol Cell Biol

1,232

1,003

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The accurate transition from G1 phase of the cell cycle to S phase is crucial for the control of eukaryotic cell proliferation, and its misregulation promotes oncogenesis. During G1 phase, growth-dependent cyclin-dependent kinase (CDK) activity promotes DNA replication and initiates G1-to-S phase transition. CDK activation initiates a positive feedback loop that further increases CDK activity, and this commits the cell to division by inducing genome-wide transcriptional changes. G1–S transcripts encode proteins that regulate downstream cell cycle events. Recent work is beginning to reveal the complex molecular mechanisms that control the temporal order of transcriptional activation and inactivation, determine distinct functional subgroups of genes and link cell cycle-dependent transcription to DNA replication stress in yeast and mammals.

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“…To go through this decision point (known as Start in yeasts), which occurs in the late G1 phase of the cell cycle, yeast cells require the activity of the mlui-binding factor (MBF) complex [1]. The MBF complex contains additional components, like the activator Rep2 [6] and the repressor complex formed by Nrm1 and Yox1 [7][8][9][10]. The MBF complex contains additional components, like the activator Rep2 [6] and the repressor complex formed by Nrm1 and Yox1 [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The INO80 complex activates the transcription of S‐phase genes in a cell cycle‐regulated manner

et al. 2018

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Chromatin structure is an essential factor in the proper regulation of DNA repair, DNA replication and transcription. The INO80 complex and the SWR complex have been shown to play a fundamental role in transcription regulation through remodeling chromatin at specific genes and loci. Here, we report that the Schizosaccharomyces pombe INO80 complex physically interacts with the mlui-binding factor (MBF) complex. Furthermore, we are able to detect the INO80 complex in MBF-regulated promoters. Binding of INO80 to these genes is cell cycle regulated, with a maximum binding preceding their transcription and accumulation of their mRNAs. In fact, the INO80 complex is required to fully and timely activate the transcription of these genes. We also show that the accumulation of acetylated H2A.Z at the +1 nucleosome is cell cycle regulated. Cells in which H2A.Z acetylation is abolished still have some cell cycle-regulated transcription of MBF-dependent genes, although to a much lesser extent.

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A homeodomain transcription factor regulates the DNA replication checkpoint in yeast

Cited by 14 publications

References 32 publications

Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1/S genes

Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1/S genes

Control of cell cycle transcription during G1 and S phases

The INO80 complex activates the transcription of S‐phase genes in a cell cycle‐regulated manner

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