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Functional connection between the Clb5 cyclin, the protein kinase C pathway and the Swi4 transcription factor in

Ethel Queralt1, J Carlos Igual

  • 1Departament de Bioquímica i Biologia Molecular, Universitat de València, C/Dr. Moliner 50, E-46100 Burjassot, Valencia, Spain.

Genetics
|August 25, 2005
PubMed

Insights

The study reveals a functional link between Clb5 cyclin, the PKC pathway, and Swi4 transcription factor. These components are crucial for maintaining DNA integrity and cell wall integrity in yeast.

Area of Science:

  • Cell Biology
  • Molecular Genetics
  • Yeast Genetics

Background:

  • The Swi4 transcription factor plays a role in cell cycle regulation.
  • The cyclin Clb5 is involved in cell cycle progression.
  • The Protein Kinase C (PKC) pathway is essential for cell wall integrity.

Purpose of the Study:

  • To investigate the functional relationship between Clb5, the PKC pathway, and Swi4.
  • To identify genes interacting with Swi4 using a synthetic lethal screen.
  • To elucidate the roles of Clb5, PKC, and Swi4 in DNA and cell integrity.

Main Methods:

  • Synthetic lethal screening to identify interacting genes.
  • Genetic analysis of mutant strains (clb5, swi4, pkc1, slt2, rad9).
  • Phenotypic analysis including cell cycle arrest, DNA integrity assays (chromosome loss, mitotic recombination), and sensitivity to various stressors (hydroxyurea, SDS, CFW, latrunculin B, zymolyase).

Main Results:

  • The rsf12 mutation, identified as CLB5, interacts with Swi4.
  • clb5 swi4 mutants arrest at G(2)/M with DNA damage checkpoint activation, showing defects in DNA integrity.
  • The PKC pathway rescues clb5 swi4 growth defects, and pkc1/slt2 mutations are synthetic lethal with clb5, indicating a connection.
  • Clb5, PKC pathway, and Swi4 are all implicated in DNA integrity control, with synthetic interactions observed with rad9 and sensitivity to hydroxyurea.
  • clb5 mutants exhibit hypersensitivity to cell integrity stressors, suggesting a role for Clb5 in cell integrity.

Conclusions:

  • Clb5 cyclin, the PKC pathway, and Swi4 transcription factor are functionally interconnected.
  • These components play critical roles in maintaining both DNA integrity and cell integrity.
  • The findings reveal a complex regulatory network involving cell cycle progression, DNA repair, and cell wall maintenance.

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