Abstract

Cell-signaling pathways are essential for cells to respond and adapt to changes in their environmental conditions. The cell-wall integrity (CWI) pathway of Saccharomyces cerevisiae is activated by environmental stresses, compounds, and morphogenetic processes that compromise the cell wall, orchestrating the appropriate cellular response to cope with these adverse conditions. During cell-cycle progression, the CWI pathway is activated in periods of polarized growth, such as budding or cytokinesis, regulating cell-wall biosynthesis and the actin cytoskeleton. Importantly, accumulated evidence has indicated a reciprocal regulation of the cell-cycle regulatory system by the CWI pathway. In this paper, we describe how the CWI pathway regulates the main cell-cycle transitions in response to cell-surface perturbance to delay cell-cycle progression. In particular, it affects the Start transcriptional program and the initiation of DNA replication at the G1/S transition, and entry and progression through mitosis. We also describe the involvement of the CWI pathway in the response to genotoxic stress and its connection with the DNA integrity checkpoint, the mechanism that ensures the correct transmission of genetic material and cell survival. Thus, the CWI pathway emerges as a master brake that stops cell-cycle progression when cells are coping with distinct unfavorable conditions.

Highlights

  • During cell-cycle progression, the cell-wall integrity (CWI) pathway is activated in periods of polarized growth, such as budding or cytokinesis, regulating cell-wall biosynthesis and the actin cytoskeleton

  • Major control points in cell-cycle regulation occur at the G1/S transition, the G2/M transition, and the metaphase–anaphase transition, coupled with the exit of mitosis

  • The morphogenesis checkpoint has been proposed as a mechanism that blocks the cell cycle in G2/M in response to defects in the actin cytoskeleton caused by various stresses, allowing time for bud formation and growth before cell division [78]

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Summary

PKC1: A Cell-Cycle Gene?

The relationship between the CWI pathway and the cell cycle has been a remarkable aspect since the beginning of research into this pathway. Subsequent studies reported that the lethality of pkc mutant cells was due to important cellwall defects, causing cell lysis during budding [5,6]. The CWI pathway acts as a bridge to interweave the morphogenetic processes that it regulates with the cell-cycle control machinery. It acts on other aspects of the cell cycle, which are apparently unrelated to the control of the cell wall. We focus on the direct mechanisms by which the CWI pathway affects the cell-cycle control system, considering the latest advances made

The CWI Pathway and Start
SBF and Slt2
Regulation of the Subcellular Localization of Swi6 by Slt2
Regulation of the Start Repressor Whi7 by the CWI Pathway
The CWI Pathway Regulates the CDK Inhibitor Sic1
The CWI Pathway and Mitosis
The Morphogenesis Checkpoint
The CWI Pathway in the Response to DNA Damage
Slt2 and the DNA Damage Response
Pkc1 and the DNA Damage Response
Concluding

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