G1 cyclin-Cdk promotes cell cycle entry through localized phosphorylation of RNA polymerase II

Science. 2021 Oct 15;374(6565):347-351. doi: 10.1126/science.aba5186. Epub 2021 Oct 14.

Abstract

Cell division is thought to be initiated by cyclin-dependent kinases (Cdks) inactivating key transcriptional inhibitors. In budding yeast, the G1 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 S5 of its heptapeptide repeats. Cln3-Cdk1 binds SBF-regulated promoters and Cln3’s function can be performed by the canonical S5 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC28 Protein Kinase, S cerevisiae / genetics
  • CDC28 Protein Kinase, S cerevisiae / metabolism*
  • Cell Division / genetics
  • Cell Division / physiology*
  • Cyclins / genetics
  • Cyclins / metabolism*
  • G1 Phase / genetics
  • G1 Phase / physiology
  • Gene Expression Regulation, Fungal
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Domains
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism*
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / metabolism

Substances

  • CLN3 protein, S cerevisiae
  • Cyclins
  • Repressor Proteins
  • SBF protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Whi5 protein, S cerevisiae
  • CDC28 Protein Kinase, S cerevisiae
  • RNA Polymerase II
  • RPB1 protein, S cerevisiae