» Articles » PMID: 34648313

G Cyclin-Cdk Promotes Cell Cycle Entry Through Localized Phosphorylation of RNA Polymerase II

Overview
Journal Science
Specialty Science
Date 2021 Oct 14
PMID 34648313
Citations 31
Authors
Affiliations
Soon will be listed here.
Abstract

Cell division is thought to be initiated by cyclin-dependent kinases (Cdks) inactivating key transcriptional inhibitors. In budding yeast, the G cyclin Cln3-Cdk1 complex is thought to directly phosphorylate the Whi5 protein, thereby releasing the transcription factor SBF and committing cells to division. We report that Whi5 is a poor substrate of Cln3-Cdk1, which instead phosphorylates the RNA polymerase II subunit Rpb1’s C-terminal domain on S of its heptapeptide repeats. Cln3-Cdk1 binds SBF-regulated promoters and Cln3’s function can be performed by the canonical S kinase Ccl1-Kin28 when synthetically recruited to SBF. Thus, we propose that Cln3-Cdk1 triggers cell division by phosphorylating Rpb1 at SBF-regulated promoters to promote transcription. Our findings blur the distinction between cell cycle and transcriptional Cdks to highlight the ancient relationship between these two processes.

Citing Articles

Dual regulation of the levels and function of Start transcriptional repressors drives G1 arrest in response to cell wall stress.

Spiridon-Bodi M, Ros-Carrero C, Igual J, Gomar-Alba M Cell Commun Signal. 2025; 23(1):31.

PMID: 39819572 PMC: 11737188. DOI: 10.1186/s12964-025-02027-z.


Phosphorylation of disordered proteins tunes local and global intramolecular interactions.

Usher E, Fossat M, Holehouse A Biophys J. 2024; 123(23):4082-4096.

PMID: 39539017 PMC: 11628823. DOI: 10.1016/j.bpj.2024.10.021.


Extending the G1 phase improves the production of lipophilic compounds in yeast by boosting enzyme expression and increasing cell size.

Hao H, Yao M, Wang Y, Zhang C, Liu Z, Nielsen J Proc Natl Acad Sci U S A. 2024; 121(47):e2413486121.

PMID: 39536088 PMC: 11588078. DOI: 10.1073/pnas.2413486121.


The CDK9-SPT5 Axis in Control of Transcription Elongation by RNAPII.

Sun R, Fisher R J Mol Biol. 2024; 437(1):168746.

PMID: 39147127 PMC: 11649480. DOI: 10.1016/j.jmb.2024.168746.


Modeling the START transition in the budding yeast cell cycle.

Ravi J, Samart K, Zwolak J PLoS Comput Biol. 2024; 20(8):e1012048.

PMID: 39093881 PMC: 11324117. DOI: 10.1371/journal.pcbi.1012048.


References
1.
Wang H, Carey L, Cai Y, Wijnen H, Futcher B . Recruitment of Cln3 cyclin to promoters controls cell cycle entry via histone deacetylase and other targets. PLoS Biol. 2009; 7(9):e1000189. PMC: 2730028. DOI: 10.1371/journal.pbio.1000189. View

2.
Swaffer M, Jones A, Flynn H, Snijders A, Nurse P . CDK Substrate Phosphorylation and Ordering the Cell Cycle. Cell. 2016; 167(7):1750-1761.e16. PMC: 5161751. DOI: 10.1016/j.cell.2016.11.034. View

3.
Chymkowitch P, Eldholm V, Lorenz S, Zimmermann C, Lindvall J, Bjoras M . Cdc28 kinase activity regulates the basal transcription machinery at a subset of genes. Proc Natl Acad Sci U S A. 2012; 109(26):10450-5. PMC: 3387082. DOI: 10.1073/pnas.1200067109. View

4.
Cao L, Chen F, Yang X, Xu W, Xie J, Yu L . Phylogenetic analysis of CDK and cyclin proteins in premetazoan lineages. BMC Evol Biol. 2014; 14:10. PMC: 3923393. DOI: 10.1186/1471-2148-14-10. View

5.
Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T . Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics. 2005; 5(4):749-57. DOI: 10.1074/mcp.T500024-MCP200. View