Molecular determinants of the cell-cycle regulated Mcm1p-Fkh2p transcription factor complex

A fundamental process in biology is the mechanism by which cells duplicate and divide to produce two identical daughter cells. The fission yeast, Schizosaccharomyces pombe, has proved to be an excellent model organism to study the role that gene expression plays in this process. The basic paradigm emerging is that a number of groups of genes are expressed in successive waves at different cell cycle times. Transcription of a particular group is controlled by a common DNA motif present in each gene's promoter, bound by a transcription factor complex. Each motif and transcription factor complex is specific to the time in the cell cycle when the group of genes is expressed. Examples of this are the MBF (MCB-binding factor)/MCB (MluI cell cycle box) system controlling gene expression at the start of S-phase, and PBF (PCB-binding factor)/PCB (Pombe cell cycle box) regulation of transcription at the end of mitosis. In some cases, these transcription control systems also operate during the alternative form of cell division, meiosis.

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Regulated proteolysis of a transcription factor complex is critical to cell cycle progression inCaulobacter crescentus

Molecular Microbiology ◽

10.1111/mmi.12166 ◽

2013 ◽

Vol 87 (6) ◽

pp. 1277-1289 ◽

Cited By ~ 36

Author(s):

Kasia G. Gora ◽

Amber Cantin ◽

Matthew Wohlever ◽

Kamal K. Joshi ◽

Barrett S. Perchuk ◽

...

Keyword(s):

Cell Cycle ◽

Transcription Factor ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Transcription Factor Complex

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A Role for the START Gene–specific Transcription Factor Complex in the Inactivation of Cyclin B and Cut2 Destruction

Molecular Biology of the Cell ◽

10.1091/mbc.11.10.3411 ◽

2000 ◽

Vol 11 (10) ◽

pp. 3411-3424 ◽

Cited By ~ 7

Author(s):

Sylvie Tournier ◽

Jonathan B.A. Millar

Keyword(s):

Cell Cycle ◽

Transcription Factor ◽

Fission Yeast ◽

Single Point ◽

Cyclin B ◽

Mitotic Catastrophe ◽

Single Point Mutation ◽

Restrictive Temperature ◽

Specific Transcription Factor ◽

Transcription Factor Complex

Hyperactivation of Cdc2 in fission yeast causes cells to undergo a lethal premature mitosis called mitotic catastrophe. This phenotype is observed in cdc2-3w wee1-50 cells at high temperature. Eleven of 17 mutants that suppress this phenotype define a single complementation group, mcs1. The mcs1-77mutant also suppresses lethal inactivation of the Wee1 and Mik1 tyrosine kinases and thus delays mitosis independently of Cdc2 tyrosine phosphorylation. We have cloned mcs1 by isolating suppressors of the cell cycle arrest phenotype of mcs1-77 cdc25-22 cells and found that it encodes Res2, a component of the START gene–specific transcription factor complex MBF (also known as DSC-1). The mcs1-77 mutant bears a single point mutation in the DNA-binding domain of Res2 that causes glycine 68 to be replaced by a serine residue. Importantly, two substrates of the anaphase-promoting complex (APC), the major B-type cyclin, Cdc13, and the anaphase inhibitor, Cut2, are unstable in G2-phasemcs1-77 cells. Consistent with this, we observe abnormal sister chromatid separation in mcs1-77 cdc25-22 cells at the restrictive temperature. Mutation of either Cdc10 or Res1 also deregulates MBF-dependent transcription and causes a G2 delay. We find that this cell cycle delay is abolished in the absence of the APC regulator Ste9/Srw1 and that the periodic expression of Ste9/Srw1 is controlled by the MBF complex. These data suggest that in fission yeast the MBF complex plays a key role in the inactivation of cyclin B and Cut2 destruction by controlling the periodic production of APC regulators.

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Nsr1, a nitrogen source-regulated microprotein, confers an alternative mechanism of G1/S transcriptional activation in budding yeast

10.1101/2020.04.20.033787 ◽

2020 ◽

Author(s):

Sylvain Tollis ◽

Jaspal Singh ◽

Yogitha Thattikota ◽

Xiaojing Tang ◽

Susan Moore ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Transcription Factor ◽

Cell Division ◽

Nutrient Availability ◽

Budding Yeast ◽

Transcriptional Activator ◽

Transcription Factor Complex ◽

Commitment To Cell Division ◽

Nutrient Conditions

AbstractCommitment to cell division at the end of G1 phase, termed Start in the budding yeast Saccharomyces cerevisiae, is strongly influenced by nutrient availability. To identify new dominant activators of Start that might operate under different nutrient conditions, we screened a genome-wide ORF overexpression library for genes that bypass a Start arrest caused by absence of the G1 cyclin Cln3 and the transcriptional activator Bck2. We recovered a hypothetical gene YLR053c, renamed NSR1 for Nitrogen-responsive Start Regulator 1, which encodes a poorly characterized 108 amino acid microprotein. Endogenous Nsr1 was nuclear-localized, restricted to poor nitrogen conditions, induced upon mTORC1 inhibition, and cell cycle-regulated with a peak at Start. NSR1 interacted genetically with SWI4 and SWI6, which encode the master G1/S transcription factor complex SBF. Correspondingly, Nsr1 physically interacted with Swi4 and Swi6 and was localized to G1/S promoter DNA. Nsr1 exhibited inherent transactivation activity and fusion of Nsr1 to the SBF inhibitor Whi5 was sufficient to suppress other Start defects. Nsr1 appears to be a recently evolved microprotein that rewires the G1/S transcriptional machinery under poor nutrient conditions.Author SummaryUnicellular microorganisms must adapt to ever-changing nutrient conditions and hence must adjust cell growth and proliferation to maximize fitness. In the budding yeast Saccharomyces cerevisiae, commitment to cell division, termed Start, is heavily influenced by nutrient availability. The mechanisms of Start activation under conditions of nutrient limitation are less well characterized than under nutrient excess. To identify potential new Start regulators specific to poor nutrient environments, we screened for genes able to bypass a genetic Start arrest caused by loss of the G1 cyclin Cln3 and the transcriptional activator Bck2. This screen uncovered YLR053c, which we renamed NSR1 for Nitrogen-responsive Start Regulator. Sequence analysis across yeast species indicated that Nsr1 is a recently-evolved microprotein. We showed that NSR1 is nutrient- and cell cycle-regulated, and directly binds the main G1/S transcription factor complex SBF. We demonstrated that Nsr1 has an intrinsic trans-activation activity and provided genetic evidence to suggest that Nsr1 can bypass the requirement for normal Cln3-dependent activation of SBF. These results uncover a new mechanism of Start activation and demonstrate how microproteins can rapidly emerge to rewire fundamental cellular processes.

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